XMRV & MRV's
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XMRV Testing - how to get tested
General
Xenotropic Murine Leukemia Virus-Related Virus (XMRV) is a human exogenous gammaretrovirus that was first described in 2006.[1] Currently it is not known whether this retrovirus can cause disease, but studies are underway to investigate this possibility, particularly in patients with Prostate Cancer and Chronic Fatigue Syndrome.
XMRV is polytropic/xenotropic hybrid. [2] In August 2010, a second CFS study (Lo et al) detected a more diverse group of MLV-related sequences that more closely resembled polytropic MLV's.
"...clearly there are a bunch of different sequences. I think before we start referring to a bunch of different viruses we really need to have viruses that go with those sequences. We can say there are sequences there that look like endogenous MLVs, maybe a little different from, but we just don't have a virus yet to go with them."
On the 18th October 2010, reports of the NJCFSA Fall Conference (Oct 17, Eatontown, NJ) started to circulate the web. XMRV had been found in those patients testing positive for MLV-related viruses in Lo et al, by Frank Ruscetti of the National Cancer Institute. [5]
The Name
XMRV (Xenotropic Murine Leukemia Virus-Related Virus) was the name given to a human retrovirus that was first described in men with prostate cancer. [7] The virus is closely related to xenotropic murine leukemia viruses (MuLVs or MLVs), which are found in mice, but its sequence is clearly distinct from all known members of this group, and is not present at an endogenous retrovirus in the mouse genome.
XMRV and segments of other MLV-related viruses, have also been found in CFS patients. The segments of MLV-related viruses are more closely related to those of Polytropic mouse endogenous retroviruses than to those of XMRVs and are even less closely related to those of Ecotropic MLVs. XMRV in fact appears to be a recombinant of a Xenotropic and a Polytropic MLV. There is little genetic difference between a Xenotropic and a Polytropic; the key difference is really only in the sequences specifying the type of cell receptor they use for entry on the host cell.
The mouse version of XMRV, called xenotropic murine leukemia viruses(X-MLV)s, has been found in lab mouse strains. Whether it can infect other lab mice or wild mice, depends on if they have the necessary receptor, that would allow them to enter a cell. An endogenous retrovirus can become xentropic when the host either loses/or alters the cells receptor needed to enter a cell. Therefore it does not require the retrovirus to change.
See here for an explanation of some of these scientific terms
Proposed Name Change
Due to the difficulties with the name XMRV, and the discovery of segments of other MLV-related viruses, a name change has been proposed by those who attended the WPI Symposium. (17th August 2010) [8] The following reasons were cited for this proposal.
- This retrovirus is a human, not mouse retrovirus.
- It is the first and so far only gammaretrovirus known to infect people.
- It is clearly not an "endogenous" retrovirus (one that is present in all genomes due to ancient infection).
The proposed new name for the virus is HGRV (Human Gamma Retro Virus). The name proposed for any illness caused by this infection is HGRAD (Human Gamma Retrovirus Associated Disease).
History
XMRV was first discovered by laboratories led by Joseph DeRisi at the University of California, San Francisco, and Robert Silverman and Eric Klein of the Cleveland Clinic. This group had sought to examine if a virus might be present in prostate cancer. [9] They found XMRV in prostate cancer tissue of men with a specific genetic defect in their antiviral defence pathway. [10] As this same genetic defect had also been found in several studies into ME/CFS, researchers at the Whittemore Peterson Institute undertook a study to test for XMRV in patients. This study was the first to isolate human XMRV virus from a disease population (ME/CFS) and showed it to be blood borne and transmissible. [11]
In a later study, it was shown that XMRV infection was not dependent upon the specific genetic defect. In further experiments the WPI was able to confirm infection by XMRV in 85% (up from 67%) of the 101 patients from the original study. [12]
Since the discovery of XMRV, several studies looking at either prostate cancer patients or CFS patients, have reported both positive and negative findings from around the world. Studies in Germany, the UK, China, the Netherlands, Ireland and the USA, have been unable to detect the retrovirus, whereas a number of studies from the USA continue to find XMRV in a significant number of prostate cancer patients. XMRV has also been found in healthy blood donors.
One study from Japan, reported at the 2010 Cold Springs Harbor Retrovirus Symposium, found that XMRV was in 1.7% of those donors tested. The second study to find XMRV in blood donors was also the first to support the findings of the WPI study. Although they did not find XMRV, they found segments of MLV-realated viruses in 86.5% of CFS patients, and 7% of blood donors. XMRV has also been detected in 9.9% immunosuppressant transplant patients from Germany [13],
Classification and genome
XMRV is a member of the Gammaretrovirus genus of the Orthoretrovirinae subfamily of Retroviridae with high sequence similarity to endogenous murine leukemia viruses. XMRV was so named because its envelope gene was similar to that of xenotropic murine leukemia virus (MuLV or MLV), an endogenous MLV that infects cells from non-mouse species including humans. Similar agents are found in a wide range of mammalian species and include the porcine endogenous retrovirus, the feline leukemia virus, the koala retrovirus, and the gibbon ape leukemia virus. Gammaretroviruses are much simpler than the complex deltaviruses such as human T-lymphotropic virus (HTLV ), or the complex lentiviruses such as human immunodeficiency virus (HIV). The XMRV genome includes gag, pol, and env genes but no accessory or regulatory genes. As the name implies, XMRV is believed to have originated in mice and is the first agent of its class to be identified in humans; it likely evolved as a result of a recombination event between polytropic and xenotropic MLV. Its pathogenic potential in humans is unknown. [14]
It has a single-stranded RNA genome that replicates through a DNA intermediate. The genome, approximately 8100 nucleotides in length, is 95% identical with several endogenous retroviruses of mice, and is 93-94% identical with several exogenous mouse viruses. [15] Different isolates of XMRV from Prostate Cancer and CFS published to date show very little sequence variation and form a distinct branch following phylogenetic analysis.
Evidence that XMRV is a Human Virus
- Mapping of viral integration sites within human chromosomes. [16]
- Presence of viral antibodies in human plasma. [17] [18]
- Presence of viral proteins and nucleic acids in fresh and frozen tissue. [19] [20] [21]
Detection
A variety of methods have been employed by researchers to detect XMRV and segments of MLV-related viruses, with some more successful than others. As there is no official test for this family of retroviruses, a number of researchers have stated that multiple methods should be employed.
Isolation of infectious XMRV from prostate cancer patients has not been published, whereas infectious XMRV has been shown in infected CFS patients by passage to lymph node carcinoma of the prostate (LNCaP), a prostate cell line robust for XMRV replication. [24] [25] Plasma from these individuals also had antibodies specific for the envelope protein of this type of retrovirus.
The authors of Lombardi et al. have stated that the most sensitive blood-based assays for detection of XMRV, in CFS patients, in decreasing order are:
- Performing nested PCR for gag sequences from LNCaP cells that have been co-cultured with subject’s plasma or activated PBMCs
- The presence of antibodies to XMRV Env in subject’s plasma
- Presence of gag products by nested PCR on stimulated PBMCs or detection of viral proteins expressed by activated PBMCs with appropriate antisera
- Nested RT-PCR of plasma nucleic acid or PCR from cDNA from unactivated PBMCs
- PCR of DNA from unactivated PBMC prepared from subject’s blood.
The authors of Lo et al. used nested PCR on PBMC-derived DNA samples, targeting the MLV-related virus gag gene, using both the previously described primer sets (Lombardi et al. and the Urisman et al) and an in-house–designed primer set with highly conserved sequences from different MLV-like viruses and XMRVs. RNA was also prepared from the deep-frozen plasma samples of their patients and analyzed by RT–PCR assay.
Suggested reasons for the differing results
- Geographical differences in the distribution of MLV-related viruses.
- High levels of sequence diversity. (Divergent MLV-related viruses, when using highly specific assays, may cause variant viruses to be missed.)
- Use of a synthetic control to calibrate assay, rather than a known clinical sample.
- Currently it is unknown whether infected individuals form antibodies to the viral proteins, and if so, to which viral proteins. (Therefore the presence or absence of antibodies to MLV proteins cannot presently be used to determine whether or not an individual is infected.)
- Peripheral blood and prostate may not be the major reservoir in vivo.
- Definition used to diagnose CFS.
- Contamination with mouse cells.
- That XMRV is not a human retrovirus, but a mouse retrovirus. Please see the 22Rv1 & Du145 cell lines page.
Prostate cancer
In the initial report on XMRV, the virus was detected in cancerous prostate tissues using a microarray containing samples of genetic material from about 950 viruses. The screen indicated the presence of a gammaretrovirus-like sequence in seven of eleven tumours homozygous for the R462Q mutation, but only in one of five tumours without the mutation. After isolation and cloning of the virus, an expanded screen found it present in 40% of tumours homozygous for R462Q and in only 1.5% of those without the mutation. Additionally, a 2009 study reported XMRV infection in 23% of subjects independent of the RNase L gene variation. [26]
Two studies in Germany [27] [28] and one study from Ireland [29] have been unable to find the retrovirus in patients with prostate cancer.
A USA study found that XMRV in prostate cancer rarely transforms cells, suggestive of indirect transformation. [30] In another prostate cancer study from the USA, XMRV protein and nucleic acids were found in malignant cells. [31]
On the 17 March 2011, the Journal of Urology published the abstracts of three papers that were to be published in April. Two were positive prostate cancer studies; one detected MRV's in the prostate tissue of 4/61 patients from Japan, three of which were found to have polytropic MLV gene sequences. The one patient found positive for XMRV sequence was retested with a blood sample and found negative. [32] The second study was a positive prostate cancer study from the USA [33], and the third showed that XMRV induces host genes that regulate inflammation and cellular physiology.[34]
Chronic fatigue syndrome
In 2009, the Whittemore Peterson Institute, National Cancer Institute and Cleveland Clinic, reported in 'Science' (Lombardi et al.), the detection of XMRV in 67% of Chronic Fatigue Syndrome patients. The authors hypothesised that XMRV could be a contributing factor in the pathogenesis of CFS. [35] The patients for this study were selected using the Fukuda and Canadian definitions for CFS, and came from 12 U.S. states and Canada, including California, New York, North Carolina, Wisconsin, Michigan, Oregon, New Mexico, New Jersey, North Dakota, Texas, and Florida. This group accounted for 76 of the total samples with 25 from patients identified during the 1984 to 1988 CFS outbreak in Incline Village, Nevada. [36] Dr. William C Reeves, the former head of the CDC's CFS program, called the research exciting but preliminary, and said he was surprised that a prestigious journal like Science had published it. [37]
Four follow-up studies[39][40][41][42] failed to find evidence of XMRV in any of several hundred CFS patients or controls, however none of these have replicated the methodology used by Lombardi et al. and none have used the same criteria for selecting patients.
The reported association of XMRV and CFS published in Science generated worldwide media coverage. In further experiments the WPI was able to confirm infection by XMRV in 85% (up from 67%) of the 101 patients from the original study. [43]
Health officials put a hold on two conflicting studies
On 22nd June 2010, a journal in the Netherlands, ORTHO, leaked that the NIH (National Institutes of Health) and FDA (Food and Drug Administration) had independently confirmed the XMRV CFS findings as published in 'Science'. Confirmation had been issued by Dr. Harvey Alter of the NIH during a closed workshop on blood transfusion held on May 26-27 in Zagreb 2010, [44], and slides from the presentation are accessible online. Select 'Available Presentations', then Session 4 'Alter.pdf' ORTHO also contacted Dr. Harvey Alter for a reaction. He did not want to comment, but confirmed that a paper is soon to be published.
"Although blood transmission to humans has not been proved, it is probable. The association with CFS is very strong, but causality not proved. XMRV and related MLVs are in the donor supply with an early prevalence estimate of 3%‐7%. We (FDA & NIH) have independently confirmed the Lombardi group findings."
On 30th June 2010, Amy Dockser Marcus reported in the Wall Street Journal, that two separate Government departments had reached contradictory conclusions. One group found a link, and the other didn't. And that both papers, although accepted for publication in separate science journals, the NIH/FDA positive study by PNAS (Proceedings of the National Academy of Sciences of the United States of America ) and the CDC negative study by 'Retrovirology', had been put on hold in early June by Health Officials. [46]
"Kuan-Teh Jeang, editor-in-chief of Retrovirology, said the Switzer paper went through peer review and was accepted for publication when he got a call from the authors earlier this month. They asked that the Retrovirology paper be held."
"In an email between scientists familiar with the situation, viewed by the Wall Street Journal, a researcher said the two teams were asked to put their papers on hold because senior public-health officials wanted to see consensus—or at least an explanation of how and why the papers reached different conclusions, said the people familiar with the situation.
A spokesman for Department of Health and Human Services said the research was being reviewed. "All of these activities need to be completed in order to ensure HHS's commitment to the accuracy and relevancy of the scientific information it reports."
On 1st July 2010, the CDC released their negative paper in 'Retrovirology'. [50] However the NIH/FDA positive study remained on hold.
"Switzer says that after the FDA-NIH team submitted a paper with results different from their own, the CDC group decided to take a “scientific pause” to look at both papers, compare study methods and do additional experiments. After this review, they decided to proceed with publication—and he says no changes were made to their original manuscript."
On 10th August 2010, Mindy Kitei, of CFS Central, reported on her website that the NIH/FDA study was now back at the journal PNAS.
On the 16th August 2010, The Reno Gazette Journal reported that Dr. Judy Mikovits (WPI), lead scientist of the Lombardi et al. paper, said that their findings have been replicated and confirmed by the U.S. Food and Drug Administration, and that the paper would be out in September. Mikovits also indicated that the WPI had new, unpublished data concerning the retrovirus, XMRV, that could lead to treatment of Chronic Fatigue Syndrome, and that this research would be published by the end of the year, probably in a clinical immunology journal. [54]
“We have immune system profiles and we can tell by the immune system how the XMRV is doing the damage,” she said. “So we could have a diagnostic test to follow clinical treatment and show that people’s immune systems go back to normal. That’s the latest data that’s really amazing. That’s what we’re after.”
NIH/FDA MLV study
On Monday 23rd August 2010, PR Newswire leaked the results of the FDA/NIH study. Several different MLV gene sequences were identified in samples from 32 of the 37 patients with CFS (86.5 percent) and 3 of the 44 (6.8 percent) healthy blood donors. The study demonstrates a strong association between a diagnosis of CFS and the presence of MLV-like virus gene sequences in the blood.
“The fact that we didn’t find XMRV doesn’t bother me because we already knew that retroviruses tend to be variable. They mutate a lot, basically. This is true of HIV and HCV [hepatitis C virus]. It’s not one virus. It’s a family of viruses.”
Lo et al. studied two sets of patients, 25 patients were from an academic medical center and 12 were referred by community physicians. Of the 25 from an academic medical center, all met the 1988 Holmes CDC criteria for CFS, and 21 also met the 1994 Fukuda CDC criteria. Diagnostic criteria for the 12 sent by individual clinicians in the mid-1990s were not known. Blood samples from the 25 from an academic centre were first taken for a study in 1993, with another 4 taken 2 years later, and another 8 taken 15 years later in 2010. The results were as follows: 24/25 (96%) patients from an academic centre were positive. All 4 patients blood taken 2 years later were positive, and 7/8 patients blood taken 15 years later were positive. Of those tested 15 years later, none had recovered. [58] Finally, 8/12 (66.7%) patients referred by community physicians were also positive.
The WPI had announced finding gag sequences that reflect greater variability from CFS patients than was originally reported for XMRV, at the May 2010 Cold Spring Harbor Laboratory (CSHL) conference on Retroviruses.
Other scientists did not agree that the results from Lo et al. supported the central argument by Lombardi et al. that MLV-related viruses are associated with CFS.
Further Studies at the XMRV Conference
At the Q&A on day 2 of the 1st International XMRV Conference, on the 8th September 2010, 4 more positive studies were mentioned. Another from the WPI, using UK patients, and three poster presentations. According to Dr Paul Cheney another 4 negative studies were also presented. [61] Dr Judy Mikovits also reported that an issue with sample preparation had been discovered by the blood working group in the last two weeks, and that it may explain the different results between studies.
At the conference Dr Frank Ruscetti (NCI) stated that some patients have more than one variety of MLV-related retrovirus.
The UK "Ashford 50" Study was presented at the conference. Blood samples from 50 UK ME/CFS patients were drawn at Ashford hospital London in April 2010 and sent to the National Cancer Institute USA for testing. Reference: Abstract O_13 http://regist2.virology-education.com/abstractbook/2010_8.pdf This was the first study showing that MLV viruses were present in the United Kingdom.
Further Studies Post XMRV Conference
On the 13th September 2010, the fifth negative study was published in Virology Journal. This study looked at 65 CFS patients in China, and 65 normal individuals out of 85 controls. They used real-time PCR or RT-PCR. [64] It is unknown if this is one of the 4 negative studies presented at the XMRV Conference, and highlighted by Dr Cheney.
On the 11th October 2010, the sixth negative study was published in Infectious Diseases Society of America. [65] This study looked at 293 people with different diseases. Of those 293, 32 had CFS using the Empiric definition - but later claimed to be Fukuda definition. [66] They used PCR & nested PCR. As with every other negative study, the test was calibrated to a synthetic version of XMRV, and not the wild version.
Mikovits at the NJCFSA Fall Conference
On the 18th October 2010, reports of the NJCFSA Fall Conference (Oct 17, Eatontown, NJ) started to circulate the web. XMRV had been found in those patients testing positive for MLV-related viruses, by Frank Ruscetti of the National Cancer Institute. [67] [68]
Blood Products Advisory Committee (BPAC) Meeting
At the BPAC meeting on the 14 December 2010, Phase II results of the Blood Working Group were announced.[69] Dr. Jonathan Stoye, presented a summary of current research on MLV-related human retroviruses and disease association. After this presentation, Christopher Cairns, who writes the Patient Advocate blog, questioned Dr. Stoye on what had happened to the 100 samples of American patients sent to Dr Kerr by Dr Enlander for use in a study. At the time Kerr was presumably working on an XMRV study with Stoye, Groom et al., which was published in February 2010. [70]. Stoye was unable to answer the question, and was not certain what had happened to those samples. [71]
Timetable of events:
- Nov 2009: Samples had started to be collected.
- Jan 2010: Stoye suggests they had all samples from Kerr by this point, but not clear if that included 100 American samples.
- 11 Jan 2010: Groom et al. Received by publisher.
- 15 Feb 2010: Groom et al. Accepted for publication.
- 15 Feb 2010: Groom et al. published
During the BPAC meeting, Dr Mikovits also spoke of how longitudinal studies on patient samples concorded with the immune responses.
Four papers published in Retrovirology on contamination
On the 20 December 2010, 4 papers together with an accompanying article were published in the journal retrovirology. One was a prostate cancer study (Robinson et al.) looking at patients in the UK, Thailand and Korea, which found that samples had been contaminated. [73] The second (Oakes et al.) was a CFS study from the USA, which also found samples had been contaminated. [74] The third was a study from Japan (Sato et al.) which had been initiated by strange results from a CFS pilot study. These researchers discovered that a RT-PCR kit from Invitrogen (Superscript II RT and Platinum Taq), was contaminated with RNA derived from polytropic endogenous MLV (PmERV), a mouse monoclonal antibody. This test kit had been used by Lo et al., in the second positive MLV-related retrovirus study. [75]
The fourth study, from the UK (Hue et al.), looked at issues that might cause contamination. In particular they suggested the XMRV clones identified in previous studies, probably originated in a prostate cancer cell line called 22Rv1. A cell line is a permanently established cell culture that will proliferate indefinitely given appropriate fresh medium and space. In the case of 22RV1, it comes from a prostate cancer patient in 1993 (Pretlow et al, 2003). The authors of Hue et al. stated that they believe XMRV is a laboratory contaminant. However, this is false. The virus expressed by the 22RV1 cell line is XMRV (Knouff et al, 2009). These cells naturally express XMRV, and XMRV is found integrated into the DNA of these cells at about ten copies per genome (Knouff et al, 2009). The authors also claim sequences of XMRV expressed in the 22RV1 cell line are ancestral to the sequences found in XMRV sequences recently found in prostate cancer patients, which is true. The fact that the sequences of XMRV in these cell lines is ancestral to XMRV isolated some 17 years later is actually clear evidence of XMRV replicating, and naturally changing over time, as a result of reverse transcriptase, and provides direct evidence contradicting the hypothesis that XMRV is a laboratory contaminant. Further evidence belies the hypothesis that XMRV is a contaminant, including studies which have mapped integration of XMRV in prostate cancer DNA into cancer-suppressing or -causing genes (Dong et al, 2007; Kim et al, 2008). The presence of integrated DNA means that it is not a contaminant. Furthermore XMRV proteins have been detected in prostate cancer patients (Schlaberg et al 2009). These authors demonstrated that IHC increased detection rates by 400% compared to PCR. And Arnold et al. (2010) demonstrated the presence of antibodies to XMRV using FISH serology in prostate cancer patients who were otherwise healthy. Arnold and others also demonstrated that FISH improved detection rates by over 400% compared to PCR. [76]
In summary none of the four papers were able to show that the positive studies were caused by contamination. And all four of the studies were accepted for publication on the 20 December 2010, and published that same day.
Also on the 20 December 2010, a press release was issued by the Wellcome Trust to say that ME/CFS is not caused by XMRV. [77] The Wellcome Trust had part funded Hue et al. [78] This story was also picked up by news outlets across the world, including the BBC [79], The Independent [80], The Guardian [81], NHS Choices website [82], TWiV [83], Medpage Today [84] and many more.
However, the belief that XMRV was a contaminant was not supported many scientists in the field. Including John Coffin, co-author of two of the four papers, Oakes et al. and Robinson et al.
Over the next several days thousand of people across the world began to voiced their dismay and disgust at this attempt to silence further research into the disease. This prompted the NHS to rename their article from the previous title 'Chronic fatigue syndrome 'not virus' to 'Chronic fatigue syndrome virus doubt'. [86]
Host of the virology blog TWiV, Vincent Racaniello (virologist), also received many responses from those alarmed by the tone of his article on the publication of the four studies, 'Is XMRV a laboratory contaminant?', and his quote that had appeared in the Chicago Tribune.
Eventually co-discoverer of XMRV Eric Klein commented on the TWiV blog, and corrected a vital point that Racaniello had either never seen or forgotten about.
This information prompted Racaniello to rewrite his blog and retract to his statement to the Chicargo Tribune. [89]
On the 21 December 2010, Annette Whittemore and Dr Judy Mikovits appeared on Nevada Newsmakes, where they also confirmed Dr Coffin's opinion that the four papers had not proven that XMRV is a contaminant. Video Transcript
Close of 2010
On the 22 December 2010, a negative CFS and MS study from Germany (Hohn et al.) was published. The authors used PCR methods which they had employed in two other studies that also failed to detect MLV-related retroviruses. [90] One of these was a collaboration with the CDC, Switzer et al.
On the 22 December 2010, a review on the 1st International XMRV Workshop, by Stoye, Silverman (co-discoverer of XMRV), Boucher and Stuart Le Grice, which had been published on the Centre for Cancer Research website on the 17 December 2010 (part of the National Cancer Institute), was published in the journal Retrovirology. [91]
On the 23 December 2010, the BMJ parroted the Wellcome Trust press release and the news coverage in an attempt to also halt this research. [92]
On the 23 December 2010, Mindy Kitei published an interview with John Coffin on CFS Central. [93] Kitei asked Coffin if he had tested the 22Rv1 prostate cancer cell line for contamination, Coffin replied that he had, and it was negative. He also reaffirmed that it is the standard positive control for XMRV. Kitei also asked whether he would be testing any of the samples from Lombardi et al. or Lo et al. for contamination. Coffin said that Tufts University had no plans to do so, but that a group he was involved with at the NCI would be and that they would use the same assay Coffin had used in his last two papers, Robinson et al. and Oakes et al.
2011
On the 7 January 2011, the UK HPA (Health Protection Agency) updated its information on Infectious Disease Surveillance.
Despite the increase in XMRV-related research there is still no consensus on the origin of this virus, whether there is any association between the presence of XMRV and any human disease effects, and the extent to which it is prevalent in the human population. Central to this uncertainty has been the lack of standardised methods for detecting viral nucleic acid and antibodies, as well as “gold standard” reference samples with which researchers can assess the specificity and sensitivity of their methods. The importance of careful validation of tests was highlighted in a series of papers in December 2010. These provided evidence that contamination of samples or reagents with ubiquitous mouse DNA has occurred in a variety of ways. Previous study results that suggested the presence of XMRV in humans may therefore be incorrect. Future assessments of the prevalence of XMRV should include more rigorous PCR and phylogenetic tests to exclude the possibility of contamination. Smith, Retrovirology December 2010 (and other papers in this issue)"
On the 25 January 2011, it was discovered that the 'CDC Foundation', had a new 'infectious disease' program called 'Synthesis of XMRV Peptides'.
To develop a mass spectrometry method that can be used to identify and quantify a novel protein produced by the prostate-cancer-associated retrovirus XMRV in patient samples.
- Funding Partners: Emory University School of Medicine
- Program Partners: CDC's National Center for Emerging and Zoonotic Infections"
On the 4 February 2011, a negative study looking for XMRV and other viruses in cerebrospinal fluid of 43 CFS patients was published. [96]
On the 16 February 2011, two studies were published. One showed that Peripheral Blood Mononuclear Cells (PBMCs) were potentially a good source for XMRV [97] The other looked at Rhesus macaques infected with XMRV. Showing that after about a month XMRV was undetectable in blood, but at 9 months XMRV viremia was reactivated, confirming the chronicity of the infection.[98]
Post PACE Trial publication
On the 18 February 2011, the PACE trial was published in The Lancet. [99]
On the 22 February 2011, the NIH hosted three video-cast presentations on the web. [100] The first two, from Dr Lo [101] and Dr Alter [102], covered MRV research. The third, from Dr Gill, was outdated, echoing the current thinking of the CDC and CAA. [103]
"...and the way the clinical sample being prepared, and the processing of this, all can make a difference."
"And even more possible to me is that there is a variation of the PCR protocol, although everybody says we are following the same PCR assay, but if you look into all the detail, the cycles are different, annealing temperature slightly different, magnesium concentration slightly different. All of this, we really don't know how much that's going to make the difference. Today the topic is, is there a virus or not? is the virus responsible, or the causative agent of this, or not? That's all very far away at the present time because, when we are looking at this, we obviously are dealing with a very low rate of infection - a very low copy number in the blood, and many of these difference can certainly result in the PCR disparities"
"They had a negative one and then sent to us to test it. I say the CDC group of patients, most of their are negative in our hands."
On the 22 February 2011, the tenth negative study looking at patients with CFS was published. Again, unvalidated assays were used. It was a joint study by the CDC and Co-operative diagnostics. [107]
On the 25 February 2011, Retrovirology published another contamination paper from Greg Towers on behalf of the Wellcome Trust and the MRC. This time they claimed that previous prostate cancer studies were the result of contamination. [108]
CROI 2011
On the 27 February to the 2 March 2011, the 18 CROI conference was held in Boston. [109] Prior to the start of the conference XMRV Global Action reported on facebook that Andrea Whittemore had communicated that Mikovits and the Ruscetti's were not invited, and their abstracts not accepted for CROI. Frank Ruscetti was however to have an abstract at the conference on the creation of a new cell line for the detection of MRV retroviruses. [110]
"Update: We’d like to clarify the information above. We have confirmed that the Ruscetti/Mikovits work on how XMRV affects the immune system was submitted and NOT accepted for presentation at CROI. At least one paper, authored by Dr. Ruscetti was accepted."
On the 1 March, one abstract, Pathak et al, stated that XMRV probably originated through recombination between two endogenous mouse viruses during passage of a human prostate cancer xenograft [112] [113]
"The early xenografts are XMRV negative, the late xenografts from the cell lines are XMRV positive. So since the early xenografts do not contain XMRV, XMRV is not required to maintain and propagate the prostate cancer cells. In addition, if replication competent XMRV was present in these original xenografts we would have expected it to spread to all of the cells in the xenograft and that was not observed. Making it very likely that these early xenografts did not contain replication competent XMRV."
"So the early xenografts do not contain XMRV, but they do contain PreXMRV-1 and 2"
"PreXMRV-1 and 2 are XMRV related proviruses, that are present in some nude mouse strains. PreXMRV-1 is replication defective, PreXMRV-2 the gag pol and env reading frames are open, and some earlier and late xenografts contain one or both of these proviruses."
"So taking this together the most likely explanation is that a recombinantion event between preXMRV-1 and preXMRV-2 generated XMRV sometime between passage seven of the xenograft and these late xenografts, between 1993 and 1996"
PATHAK - "The recombination event is unique, so the infection event would have to occur during the in vivo passage of the tumour, since it occurred before the cell line. Now, as we have discussed to exclude that possibility you would really have to characterise all mice in the world genetically, so the answer is no I can't exclude that possibility"
KEARNEY: "Well, I can't say. I think there it could be multiple sources if contamination is the issue, there could be multiple sources for contamination, either from 22Rv1 cells, from virus, from mouse genomic DNA."
TOWERS: "Ok, but the sequence of the supernatent virus is identical, whereas the sequences of the cell DNA virus is a few changes?"
KEARNEY: "Well, actually that is not what we saw. We did single genome sequencing from cells from the 22Rv1 cells and we found only two genomes that were hypermutated and the rest were almost identical to what was in..."
TOWERS: "Almost?"
KEARNEY: "They were, essentially identical with maybe a single nucleotide change in one of the sequences..."
TOWERS: "Ok, so this 20 provirus I guess with maybe identical sequencing"
KEARNEY: "I think we did a total of 42 sequences"
UNKNOWN: "And that was GAG?"
KEARNEY: "That was GAG."
CINGOZ: "Actually currently the ongoing experiments are trying to figure out whether this virus, PreXMRV-2 is infectious by itself. When you just look at the full length sequence it seems to have open reading frames that are intact. So there seems to be no reason for it not to be infectious. However, we haven't done the experiment yet, so I don't have any results on that. Does that answer the question? And the other thing is... the Xenotropic, it has Xentropic LTRs like XMRV even though the sequence is a little different. However, the envelope is Polytropic unlike XMRV, so there could be differences there at least in the host tropism."
STOYE: "Could I add just, there is another interesting to me, facet of the biology of XMRV, it is dually sensitive to both FE1M and FE1B. I think there is going to be a fair amount of study of the biology of the virus, it is quiet an interesting virus, your right. But I think there is going to be less and less interest in studying its association with disease.
JONES: "Yea, I can agree. I know a lot of people who were working on just the basic biology of the virus. Particularly people who have worked with these mouse viruses for a number of years, and it does seem to be behaving differently. And I guess it is worth mentioning, I guess we have said this but, in regards to Greg's question, I mean this is, at least in culture, this is a replicating virus that can cause a productive infection in primary human cells in addition to cell lines and you can pass it to other cells. And as you said, and as Jonathan said it is different from a lot of known MLVs. So from a basic science prospective there is some interest in this virus."
BASHAM: "My question, San Francisco, just sort of following up on that. I think there is no doubt after this meeting that this virus arouse from a recombination as that original prostate tumour was explanted and propagated and it's extraordinarily infectious in vitro and clearly it is demonstrating infectivity in human x-plants in a variety of human cell lines. It can transmit into non-human primates. And I'm a little concerned, you know one this was human created through... in the laboratory and it's a highly infectious retrovirus and could it transmit to humans. Could it have subsequent to the event transmitted to humans. We've been doing studies using pedigreed negative controls, some of whom happen to be lab workers who are working with this virus who intermittently score positive in one lab or another and I've just ignored that but now I'm beginning to be a little concerned that might there be transient infections of humans. Has anyone embarked on studies to look at either nucleic acid or serologic detectability in lab workers who have or are working with these cell lines and ex-cetera?"
JONES: "I do know of some animal studies where the lab handlers are being monitored. I don't think anyone in the laboratory is...there's ethical reasons I think not to test each other."
STOYE: "One, I can talk about an anecdote among urologists in Britain who were suddenly alarmed that this cell line that they had been using was loaded with virus. I think there are some of us that have been working with XMRV or related viruses for... well I have been doing it for 35 years or something, and I know I'm negative or at least I was the last time I looked."
SWITZER: "I just wanted to add to that, we share your concern Mike and we have started a study looking at some archived specimens that we have from laboratory workers that we screened and found other simian retroviruses in for example, that we are going to look for XMRV evidence of other MuLVs."
Post CROI 2011
On the 9 March 2011, another negative CFS paper from Myra McClure was published in PLoS One. [120] This again used PCR to look at 48/186 patients used in her earlier CFS study Erlwein et al. [121] , and included two ELISA assays that had previously been used in Hohn et al. and had not detected the virus.
Pathogens in the Blood Supply
On the 29th March 2011, Mikovits and Lipkin gave web presentations for Pathogens in the Blood Supply. A conference hosted by The New York Academy of Sciences. [122] During the presentation Mikovits was asked whether she had any concerns about the 22Rv1 cell line, that had been suggested as the source of contamination for XMRV.
Mikovits also talked about the P and X strains of XMRV, Lo et al, and the primers used in Lombardi et al.
State of Knowledge Workshop (NIH)
On the 7 and 8 April 2011, the Trans-NIH ME/CFS Research Working Group held a conference to identify gaps in research into ME/CFS. Two patient advocates, Mary Schweitzer and Pat Fero, were nominated by the community to help in planning the event and the CFIDS Association of America were automatically included in the committee, for reasons unknown, with both Kim McCleary and Suzanne Vernon also attending the event. Several excellent presentations were given by Leonard A. Jason, Kenneth J. Friedman, Mary Schweitzer and Pat Fero. The main discussion and topic however was HGRV's, which consisted of talks by Judy Mikovits, John Coffin, and was moderated by Harvey Alter one of the authors of Lo et al. Although both Mikovits, Alter and others have data showing HGRV's consist of xentropic, polytropic and modified polytropic varieties, John Coffin voiced his belief that the Xenotropic variety should be left behind as he felt his unpublished data indicated the virus had originated in the prostate cancer cell line 22Rv1 and that this cell line, although never used in the WPI lab, must have contaminated the samples from Lombardi et al. His opinion on this matter was also unable to explain the serology results from Lombardi at al and the vast difference between controls and patients in this blinded study.
MIKOVITS: "It's not sequences, it's proteins, it's antibody response."
COFFIN: "With viruses and proteins of sequences that I don't know. If we get these sequences of these other viruses into GenBank where people can look at them, then we can do some analysis."
MIKOVITS: "We put the phylogenetic analysis up there."
VERNON: "John, you are not going to be here tomorrow, I would like to pick your brain to know what you see as the next steps for XMRV and all these."
COFFIN: "I see the next step as leaving the virus that we know as XMRV behind. I don't...I just don't see...I don't see how that... Now that doesn't mean there's not another gammaretrovirus that is not sufficiently cross reactive with the primers and things that have been used to not be... I think the... I just... I think however that enough evidence has been presented that there is some infectious cause here. Maybe another retrovirus it's entirely possible that it's worth continuing to do it. I would say however that we are continuing to participate in studies like the Blood Working Group study, and the study that is enrolling and seeing patients right now at NCI. Patients are coming in, collected patients who have been told they are XMRV positive by various assays and we are going to do a very through work up on these patients, using exactly the same sort of conditions that I mentioned, where every patient is... patients and controls are brought in treated as much as possible blindly. At least every single sample that is taken is taken exactly the same set of reagents, tubes and so on and so forth. And those are going, were just going to work those up through all of the assays we have available at the NCI. And the NCI have I have to say has done a huge amount of work on this. It's taken a huge amount of resources and diverted from other things to work on this problem. Ever before since the Science paper..."
(...)
MIKOVITS: "Just that it has never been addressed the fact that all of our patients and controls and studies now, from at least six studies, from thousands of patients around the world, the patients are infected, the virus is isolated, proteins not PCR, not sequences, an immune response to multiple proteins is far more evidence that there is a human gammaretrovirus infection associated with this disease, than it is any kind of a contaminant. Especially since no infected cell line has ever been used in our laboratory."
COFFIN: "And has no cell line ever been ever used in your laboratory ever?"
MIKOVITS: "No XMRV infected cell lines"
COFFIN: "There are some lines of LNCaPs that are contaminated perhaps with this virus"
MIKOVITS: "Ours are not. We do it every single week, we do all of the tests"
COFFIN: "There are some lines of Jurkat that are contaminated, many many cell lines..."
MIKOVITS: "We don't have Jurkat growing in our laboratory where we isolated these viruses. We directly isolated from the blood."
Singh's paper published (Shine et al)
On the 4 May 2011, Ila Singh's study (Shin et al) was published.[128] Using new unvalidated assays this paper reported finding no XMRV or others MLV-related viruses in 100 CFS patients and 200 healthy volunteers. The paper stated that a clone had been used to check each assay was capable of detecting XMRV.
On the 6 May 2011, Mindy Kitei published an interview with Singh on her site CFS Central. [131] Singh made several statements that contradicted the published paper of Shin et al during this interview.
"Our prostate cancer study was entirely on prostate tissues. (...) there was no way to go back to those patients and obtain blood samples."
"For the viral culture studies, we used very small amounts of titrated virus that was grown in the lab as positive controls. And all of these positive controls were always positive."
Singh had previously stated on the 8 August 2010, in an interview with Vincent Racaniello on TWiV, that use of a synthetic sample was not sufficient to prove an assay is capable of detecting the virus in blood.
The paper Shin et al also mistakenly stated that 14 patients from Lombardi et al had also been tested. In an article in the WSJ Dr Mikovits made it clear that only 2 had come from Lombardi et al. One of these two had been used to create a full length clone and was the source for the electron microscopy image of the budding virus.[134]
On the 4 May 2011, with assistance from the CFIDS Association, Virology blog journalist Vincent Racaniello posted an article on the Singh paper (Shin et al). [137] In response to this article, Ian Lipkin, the scientist hired to conduct the multi lab study for the NIH, sent Racaniello a letter to correct his misunderstanding of the situation. [138]
We have a plethora of explanations for how CFS/XMRV/MLV studies could go awry. However, we don’t have evidence that they have. Absent an appropriately powered study representing blinded analyses by Mikovitz and Lo/Alter of samples from well characterized subjects using their reagents, protocols and people, all we have is more confusion.
I remain agnostic. We won’t have answers until the end of 2011.
The NIH will post something on our study today.
Ian"
CDC detects XMRV in prostate cancer patients
On the 4 May 2011, the CDC reported detecting XMRV in a few patients (3/162) with prostate cancer. [140] This was the first time the CDC had detected XMRV outside of the Blood XMRV Working Group.
XMRV replication in mucosal sites
On the 12 May 2011, an abstract title of 'XMRV replicates preferentially in mucosal sites in vivo: Relevance to XMRV transmission?' was posted on Retrovirology, for the 15th International Conference on Human Retroviruses: HTLV and Related Viruses, which was to be held in June 2011. [141][142] The abstract authors included Silverman and Klein, the co-discovers of XMRV. Other abstracts for the conference were also posted. [143]
XMRV-associated CFS inflammatory signature (Lombardi, 2011)
On the 13 May 2011, the journal "In Vivo" published a list of forthcoming papers, one of which was new study from the WPI, that had found a Distinct Inflammatory Signature for Xenotropic Murine Leukemia Virus-related Virus-associated Chronic Fatigue Syndrome (XMRV-associated CFS).[144][145][146] This cytokine/chemokine expression profile was found to be is highly predictive of acute onset XMRV positive ME/CFS (and vice versa) relative to healthy controls. This profile is therefore capable of being used as a diagnostic test for ME.
Another paper, also published on the 13 May 2011 in the journal of Virology, provided data on integration site for XMRV in CD4+ T cells in vitro, and found that whilst XMRV prefers to integrate into DNAse-vulnerable regions, it also likes to integrate into the outer curves of nucleosomes.[148]Forum discussion on this paper
Science publishes two questionable papers (Knox et al. & Paprotka et al)
On the 31 May 2011, two papers were released in Science Express. The first, Knox et al., was another negative study looking for XMRV in ME/CFS patients. The authors of this study had managed to obtain some samples from people who had originally been in Lombardi et al. paper. But in this study, they did not use the same methods as in Lombardi et al. and they had not clinically validated their assays.[149][150]
The other paper, Paprotka et al., purported to have found the origin of XMRV.[151][152] This study, which had been presented at CROI earlier in the year, claimed that a prostate cancer cell line called 22Rv1, which is infected with XMRV, was responsible for contaminating the positive studies. They describe how they believe that two mouse viruses, claimed to predate XMRV and which they called PreXMRV-1 and 2, must have recombined at some time during the creation of the cell line as it was passaged through lab mice. However, they were not able to show which mice were used for xenografting in the construction of 22Rv1, they were not able to show that the two viruses predate XMRV and they even detected XMRV env sequences in the earlier xenografts, which would argue against XMRV having been created during xenografting and for the patient actually having been infected with XMRV. The cell line 22Rv1 has also never been in the WPI lab, or in the state of Nevada, and in Silverman's prostate cancer studies it was in a freezer and had not been used for several years. One of the authors of Paprotka et al, John Coffin, had previously stated that low sequence diversity was also evidence against contamination, but in this paper was now claiming the opposite.
On the 26th May 2011, Science magazine, contacted the corresponding author of Lombardi et al., Judy Mikovits, and asked in an editorial expression of concern if the authors would consider retracting their paper, Lombardi et al. Mikovits held a conference call with the other authors of Lombardi et al. and they agreed not to retract the paper as it was scientifically premature to do so. [155] Annette Whittemore, President of the WPI and the clinical board of the WPI also wrote to the editor of Science magazine to voice their concerns at them issuing a editorial expression of concern.[156][157][158] This story was leaked to the media, by persons unknown, before publication of Knox et al. [159]
Millers mouse paper to be published
On the 14 February 2011, Dusty Miller gave a statement to CFS central about a study he was to have published the following day in the Journal of Virology.[161] He claimed to have found a mouse virus that was similar to PreXMRV-2 and said that part of it also matched XMRV. At the same time his student, Andy Vaughn, made several comments on Facebook regarding the unpublished paper.[162] Miller's paper was not published the following day, but Miller posted a comment on the CFS Central blog, saying it would likely appear the following week.[163]
On the 15 May 2011, the NCI released a propaganda video on the Paprotka et al., which feature Vinay Pathak and Stuart LeGrice.[164]
On the 15 May 2011, Bridget Huber had her second negative ME/CFS study published. This paper used two novel chelmiluminescence immunoassays (CMIAs) and a Western blot to test patient plasma on 112 patients and 36 healthy controls. [165]
XMRV & other diseases
Please see the wiki page on XMRV & other diseases
Contamination claims
Some have claimed that the positive results are the cause of mouse contamination. However, this has been rigorously ruled out by testing at all stages for mouse contamination and using non mouse labs. Now certain people have tried to claim that XRMV is the contamination and that it has come from infected cell lines. However, Lombardi et al has never used the infected cell lines in their experiments and those cell lines have never been in their lab.
Please see the 22Rv1 & Du145 cell lines page for more details on the infected cell lines.
Contamination Assays
IAP assay
John Coffin's lab developed a new mouse contamination assay based on intracisternal A particle (IAP), a repeated element that presents about 1,000 copies per mouse genome. Coffin claims that the test can detect mouse DNA contamination in many samples where mitochondrial DNA doesn't. However others such as Lo, believe that the mitochondria PCR assay is much more sensitive in detecting the mouse DNA. [166] It is also possible that, as this assay has not been validated, that it may be producing false positives, either though identifying human IAPs instead of only mouse IAPs, or thorough the transference of mouse IAPs to humans via mouse viruses.
It is also interesting to note that Lo has retested his samples using the unvalidated IAP assay, but has found no contamination.
Epigenetic's
Epigenetic responses to MLV infections will change with time as genes are manipulated.
Immune System
APOBEC3G
APOBEC3G is an antiviral defence protein that attacks viral RNA, and changes its sequences specific location. Groom and Paprotka have reported that cell lines that express APOBEC3G reduce the titre of infectious XMRV, when they were put in cell lines that didn't express APOBEC3G. [168][169] On the 29 march 2011, Mikovits reported at the Pathogens in the Blood Supply webinar, that following integration into PBMC chromosomes, provirus whose RNA has been attacked by APOBEC3G should exhibit G to A hypermutation. That they had tested XMRV and found considerable hypermutation, and consequently this was further evidence that XMRV is a human infection, because the anti viral defence mechanism is occurring. They also had shown that the hypermutation was between 2 to 7%, which is not 99% similar, which the six samples in the gene bank represent. Next they also tested whether this edited XMRV could still make infectious virus and showed it could. [170]
Co-pathogens
Transmission
XMRV is closely related to several known xenotropic mouse viruses. These viruses recognize and enter cells of non-rodent species by means of the cell-surface xenotropic and polytropic murine leukemia virus receptor (XPR1). Several authors have speculated that XMRV could be sexually transmitted. [171][172][173] Both cell-associated and cell-free transmission were reported in vitro by Lombardi et al. [174] The virus has also been found in respiratory tracts and respiratory secretions of infected individuals[175]
Judy Mikovits of the Whittemore Peterson Institute has stated that XMRV has "almost certainly entered the U.S. blood supply system, but did not know whether it would be susceptible to the same heat treatments that successfully kill off the AIDS virus in blood products." [176] A United States federal consortium is now working to determine the prevalence of XMRV in the blood supply and the suitability of different detection methods.[177][178]
On the 26 May 2011, Advances in Virology published a paper from Silverman and Klein that showed VP62 XMRV displays 'tissue tropism'. It readily infects some tissues and not others. This research used IHC and FISH, methods that are not prone to contamination error. [179]
Infectious
Infectious XMRV has been identified in ME/CFS by Lombardi et al. and by Frank Ruscetti in an unpublished prostate cancer study. [180] XMRV has also been shown to still be infectious despite the APOBEC3G antiviral defence protein. [181]
MLV viruses can be spread through saliva. XMRV may also be spread this way, and it has been highlighted that it could also be aerosolised.
The issue of transmission is being studied. An abstract with the title, 'XMRV replicates preferentially in mucosal sites in vivo: Relevance to XMRV transmission?' has been submitted for the 15th International Conference on Human Retroviruses: HTLV and Related Viruses, which is to be held in June 2011. The abstract authors included Silverman and Klein, the co-discovers of XMRV. [182]
XMRV is capable of infecting lab mice
Originally mouse X-MLVs (Xenotropic MLVs) were defined by their inability to infect cells of their natural mouse hosts. It is now clear that X-MLVs actually have the broadest host range of the MLVs. Nearly all nonrodent mammals are susceptible to X-MLVs, and all species of wild mice and several common strains of laboratory mice are X-MLV susceptible. [183]
XMRV can infect cells other than those expressing XPR1
XMRV can use the cell surface receptor XPR-1 (xenotropic and polytropic retrovirus receptor 1) to gain entry into cells. XPR-1 is found in a diverse array of tissues: lymphocytes, hepatocytes, as well as cells in the brain, pancreas, kidney, prostate, and muscle. It has also been demonstrated that XMRV can use alternative receptor(s) and/or mechanism(s) to gain entry. [184]
Blood Donation
The association of XMRV and CFS reported in 'Science' prompted Health Canada,[185][186] the New Zealand Blood Service,[187] and The Australian Red Cross Blood Service[188] in 2010, to ban blood donations from individuals with CFS. On June 18th 2010, the American Association of Blood Banks, recommended actively discouraging potential donors who have been diagnosed by a physician as having CFS from donating blood or blood components.[189] On the 4th September 2010, Times of Malta, reported that the National Blood Transfusion Services for Malta were also deferring patients with a history of ME from donating blood.[190]
In the United Kingdom patients cannot give blood until they have recovered. This ban has been in place since at least 1989, and is not specific to XMRV. [191] [192] On the 13th August 2010, an interent blogger published a letter from the Department of Health (UK) stating that a lifetime blood ban would be soon put in place. [193] On the 27 August 2010, the ME Association, after contacting the Department of Health, confirmed that from the 1st November 2010, those who have had ME/CFS would be permanently excluded from donating blood. [194] More details on the history of this announcement can be found on the United Kingdom wiki page, under the 'Blood Donations' section.
On the 3 December 2010, the American Red Cross announced that they would defer indefinitely any donor who reveals during the donor interview that they have been diagnosed with CFS. [195]
On the 10 December 2010, the Norwegian Directorate of Health introduced a ban on ME/CFS patients from donating blood due to the finding of MLV-related retroviruses.[196]
On the 14 December 2010, at the Blood Products Advisory Committee Meeting on the 14, the Food & Drug Administration (FDA), USA, asked the Blood Products Advisory Committee (BPAC) to vote on whether the scientific data support asking donors about a medical history and/or diagnosis of CFS as a basis for indefinite deferral. The panel voted 9 to 4 in favour of indefinite deferral of CFS patients based on all evidence that it will promote donor and recipient safety. This recommendation will now be reviewed by the FDA, which typically follows the advice of such panels but is not required to do so. There is no timetable yet on a final decision. [197][198]
On the 14 April 2011, the MEA reported that the Irish Blood Transfusion Service had permanently banned blood donations on the 9 August 2010 from those with a current or previous diagnosis of CFS because of XMRV.[199][200]
On the 17 May 2011, slides from a presentation on XMRV by Indira K. Hewlett, Ph.D (Chief, Laboratory of Molecular Virology, DETTD/CBER/FDA) to the XXII SoGAT meeting (14/15 April 2011) were circulated on the web.[201]
SUMMARY:
- Canada - any donor who has a medical history of CFS will be indefinitely deferred from donating blood. (6 April 2010) [202]
- New Zealand - patients with a diagnosis of CFS are permanently deferred. (April 2010) [203]
- Australia - will indefinitely defer donors who have been diagnosed with CFS diagnosis. (23 April 2010) [204]
- USA - its member blood collectors, through the use of donor information materials available at the donation site, actively discourage potential donors who have been diagnosed by a physician with CFS [also known as chronic fatigue and immune dysfunction syndrome (CFIDS) or myalgic encephalomyelitis (ME)] from donating blood or blood components. [205]
- Malta - deferring donors permanently if they have a history of Myalgic Encephalomyelitis (ME). (4 September 2010) [206]
- UK - blood donors who report that they have had ME/CFS will be permanently excluded from giving blood in the UK. [207] (Mentioned 13 August 2010, Implemented 1 November 2010) [208]
- USA - The American Red Cross will defer indefinitely any donor who reveals during the donor interview that they have been diagnosed with CFS. [209]
- Norway - Those with a ME/CFS diagnosis are banned from donating blood. [210]
- USA - FDA Blood Products Advisory Committee (BPAC) voted to recommend indefinite deferral of CFS patients based on all evidence that it will promote donor and recipient safety. This is to be achieved by asking donors about a medical history and/or diagnosis of CFS [211][212]
- Ireland - Irish Blood Transfusion Service: Permanently excluded from donating blood if you have a current or previous diagnosis of CFS. To protect the donor and recipient's health due to XMRV. [213][214]
1st International XMRV conference
The 1st workshop on XMRV is to be held on the 7-8 September 2010, at the National Institutes of Health in Bethesda, Maryland, USA, and will cover pathogenesis, clinical and public health Implications. [215]
Click here to see further details of the 1st International XMRV conference
- 'Abstract Book: 1st international workshop on Xmrv' (Journal of abstracts and conference reports from international workshops on infectious diseases & antiviral therapy, Volume 8, 7-8 September 2010)
- Online PDF Presentations (7-8 September 2010)
USA Multi-Center Study
On the 8th September 2010, the WSJ reported that NIH director Francis Collins had asked Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases, to direct a multi-center study of CFS patients to try to get to the bottom of the conflicting papers. In the same article, Fauci pointed toward the use of different patients for the discrepant results, and said that he had asked W. Ian Lipkin, a professor of epidemiology at Columbia University’s Mailman School of Public Health, to head up the study. Lipkin also noted that the way labs process the blood samples or the tests they use, could also be a contributing factor. [216]
The study will involve fresh blood samples from 100 CFS patients and 100 similar, but healthy people — 25 of each group from four different sites around the country, to provide geographic diversity. The samples will be processed, blinded and sent to the FDA, the CDC and the Whittemore Peterson Institute. If a lab finds a sample is positive for XMRV, further tests will be needed to confirm the result. If one lab finds a positive sample but another lab doesn’t, the same samples can be shipped again, with a new blinded code, to be tested again. If a lab gets the same result, it is valid.
Lipkin has stated that, it may turn out that certain labs are simply more proficient than others at finding XMRV and related viruses.
Testing
Dr Judy Mikovits has indicated that the WPI is now working on a test to measure how the immune system is functioning, thereby allowing them to assess the effectiveness of any treatment.
Treatment
Currently three antiretrovirals have shown promise in vitro (in the lab): Zidovudine (AZT), Tenofovir and Raltegravir.
More info can be found on the Antiretroviral Therapy page.
Treatment Possibilities for the New Human Retroviruses
Links
ME or CFS Research Studies
- 'Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome' Lombardi et al. (Science, 8 October 2009)
- 'Supporting Online Material for Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome' Lombardi et al. (Science, 8 October 2010)
- 'Response to Comments on "Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome"' Mikovits JA and Ruscetti FW (Science, 14 May 2010)
- 'Distribution of Xenotropic Murine Leukemia Virus-Related Virus (XMRV) Infection in Chronic Fatigue Syndrome and Prostate Cancer' Mikovits et al. (AIDS reviews, July - September 2010, Volume 12 - Number. 3)
- 'Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome' Mikovits et al. (Landesbioscience, August 2010)
- 'Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue Syndrome' Erlwein et al. (Plosone, 6 january 2010)
- 'Absence of xenotropic murine leukaemia virus-related virus in UK patients with chronic fatigue syndrome' Groom H (Retrovirology, 15 February 2010)
- 'Prevalence of xenotropic murine leukaemia virus-related virus in patients with chronic fatigue syndrome in the Netherlands: retrospective analysis of samples from an established cohort' van Kuppeveld et al. (25 February 2010)
- Letter to the Editor: Judy A. Mikovits, PhD, Director of Research, Whittemore Peterson Institute, Reno, Nevada Mikovits (Bulletin of the IACFS/ME, 6 May 2010)
- Response to Comments on “Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome” Mikovits & Ruscetti (Science, 14 May 2010)
- 'Presentation to the IPFA/PEI 17th Workshop on "Surveillance and Screening of Blood Borne Pathogens' Harvey Alter (IPFA, Zagreb, 26-27 May 2010)
- 'Absence of evidence of Xenotropic Murine Leukemia Virus-related virus infection in persons with Chronic Fatigue Syndrome and healthy controls in the United States' Switzer et al. (Retrovirology, 1 July 2010)
- 'Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors' Shyh-Ching Lo et al. (PNAS, 23 August 2010)
- FORUM THREAD Lo et al Letters to the editor (PNAS, 1 October 2010) [218] [219] [220]
- 'Failure to detect xenotropic murine leukaemia virus-related virus in Chinese patients with chronic fatigue syndrome' Ping Hong et al. (Virology Journal, 13 September 2010)
- 'Xenotropic Murine Leukemia Virus–Related Virus Prevalence in Patients with Chronic Fatigue Syndrome or Chronic Immunomodulatory Conditions' Henrich et al. (J Infect Dis., 11 October 2010)
- 'XMRV:Virological, immunological and clinical correlations in a patient with Chronic Lymphocytic Leukemia' Snyderman et al. (Poster presentation at MD Anderson Cancer Center in Houston, Texas, 13 Octobers 2010)
- 'Contamination of human DNA samples with mouse DNA can lead to false detection of XMRV-like sequences' Oakes (Retrovirology, 20 December 2010)
- 'No Evidence for XMRV in German CFS and MS Patients with Fatigue Despite the Ability of the Virus to Infect Human Blood Cells In Vitro' Hohn et al. (PLoSone, 22 December 2010)
- 'Analysis of cerebrospinal fluid from chronic fatigue patients for multiple human ubiquitous viruses and XMRV' Schutzer (Annals of Neurology, 4 February 2011)
- 'Serologic and PCR testing of persons with chronic fatigue syndrome in the United States shows no association with xenotropic or polytropic murine leukemia virus-related viruses' Satterfield (Retrovirology, 22 February 2011)
- 'Investigation into the Presence of and Serological Response to XMRV in CFS Patients' Erlwein (PLoS One, 9 March 2011)
- 'No association of Xenotropic Murine Leukemia Virus-related virus with prostate cancer or chronic fatigue syndrome in Japan' Furuta (Retrovirolgy, 17 March 2011)
- 'Absence of XMRV and other MLV-related viruses in patients with Chronic Fatigue Syndrome' Shin (Journal of Virology, 4 May 2011)
- 'No Evidence of Murine-Like Gammaretroviruses in CFS Patients Previously Identified as XMRV-Infected' Knox (Science, 31 May 2011)
- 'No Evidence of Murine-Like Gammaretroviruses in CFS Patients Previously Identified as XMRV-Infected' - Materials/Methods, Supporting Text, Tables, Figures, and/or References Knox (Science, 31 May 2011)
- 'Failure to detect XMRV-specific antibodies in the plasma of CFS patients using Highly Sensitive Chemiluminescence Immunoassays' Oakes (Hindawi, 15 May 2011)
- 'Xenotropic murine leukemia virus-related virus in monozygotic twins discordant for chronic fatigue syndrome' Jerome (Diagnostic Microbiology and Infectious Disease, 25 July 2011)
- 'Phylogenetic analysis of MLV sequences from longitudinally sampled Chronic Fatigue Syndrome patients suggests PCR contamination rather than viral evolution' Katzourakis (Journal of Virology, 17 August 2011)
Research studies for other diseases
- 'Identification of a Novel Gammaretrovirus in Prostate Tumors of Patients Homozygous for R462Q RNASEL Variant' Urisman A et al. (31 March 2006)
- 'Quantification of reverse transcriptase in ALS and elimination of a novel retroviral candidate' McCormick (Neurology, 22 January 2008)
- 'Prevalence of human gammaretrovirus XMRV in sporadic prostate cancer' Fischer F (29 September 2008)
- 'No evidence of XMRV in Irish prostate cancer patients with the R462Q mutation' D'Arcy F et al. (March 2008)
- 'Lack of evidence for xenotropic murine leukemia virus-related virus(XMRV) in German prostate cancer patients' Hohn O et al. (16 October 2009)
- 'XMRV is present in malignant prostatic epithelium and is associated with prostate cancer, especially high-grade tumors' Schlaberg R et al. (8 September 2009)
- 'Xenotropic Murine Leukemia Virus–related Gammaretrovirus in Respiratory Tract' Fischer N et al. (Emerg Infect Dis. June 2010)
- 'Lack of Detection of XMRV in Seminal Plasma from HIV-1 Infected Men in The Netherlands' Cornelissen et al. (Plosone, 10 August 2010)
- Letter to the editor 'Absence of xenotropic murine leukaemia virus-related virus in Danish patients with multiple sclerosis' Maric (Journal of Clinical Virology, 9 September 2010)
- 'Prevalence of human xenotropic murine leukemia virus-related gammaretrovirus (XMRV) in dutch prostate cancer patients.' Verhaegh GW et al. (28 September 2010)
- 'Failure to Detect Xenotropic Murine Leukemia Virus–Related Virus in Blood of Individuals at High Risk of Blood‐Borne Viral Infections.' Barnes et al. (J Infect Dis., 11 October 2010)
- 'Detection of Xenotropic Murine Leukemia Virus–Related Virus in Normal and Tumor Tissue of Patients from the Southern United States with Prostate Cancer Is Dependent on Specific Polymerase Chain Reaction Conditions' Danielson et al. (J Infect Dis., 11 October 2010)
- 'PCR and serology find no association between xenotropic murine leukemia virus- related virus (XMRV) and autism' Satterfield et al. (Molecular Autism, 14 October 2010)
- 'XMRV: A New Virus in Prostate Cancer?' Aloia er al. (American Association for Cancer Research, 21 October 2010)
- 'Absence of detectable xenotropic murine leukemia virus–related virus in plasma or peripheral blood mononuclear cells of human immunodeficiency virus Type 1–infected blood donors or individuals in Africa' Tang et al. (Transfusion, 15 November 2010)
- 'Mouse DNA contamination in human tissue tested for XMRV' Robinson (Retrovirology, 20 December 2010)
- 'No Xenotropic Murine Leukemia Virus–related Virus Detected in Fibromyalgia Patients' Luczkowiak (Emerging Infectious Diseases, February 2011)
- 'No difference in antibody titers against Xenotropic MLV Related Virus in prostate cancer cases and cancer-free controls' Sabunciyan (Molecular & Cellular Probes. 28 January 2011)
- 'Lack of Infection with XMRV or Other MLV-Related Viruses in Blood, Post-Mortem Brains and Paternal Gametes of Autistic Individuals' Lintas (PLoS One, 23 February 2011)
- 'Preliminary screening of Xentropic Murine leukemia virus-related virus in Japanese prostate cancer patients' Igawa (Journal of Urology, April 2011)
- 'Xenotropic Murine Leukemia virus related virus (XMRV) is present in malignant prostate tissue but does not affect pathological or clinical outcome' Ritch (Journal of Urology, April 2011)
- 'No Evidence of XMRV or Related Retroviruses in a London HIV-1-Positive Patient Cohort' Gray (PLoSOne, 23 March 2011)
- 'No Association of Xenotropic Murine Leukemia Virus-Related Viruses with Prostate Cancer' Switzer (PLoSOne, 4 May 2011)
- 'XENOTROPIC MURINE LEUKEMIA VIRUS-RELATED VIRUS (XMRV) IS NOT FOUND IN PERIPHERAL BLOOD CELLS FROM TREATMENT-NAIVE HIV+ PATIENTS' Fabrizio (CMI, 19 May 2011)
- 'No evidence of XMRV or MuLV sequences in prostate cancer, diffuse large cell B cell lymphoma or the UK blood donor population' Robinson (Advances in Virology, May 2011)
Further XMRV research studies
- 'Multiple Integrated Copies and High-Level Production of the Human Retrovirus XMRV (Xenotropic Murine Leukemia Virus-Related Virus) from 22Rv1 Prostate Carcinoma Cells' Knouf (Journal of Virology, July 2009)
- 'The Prostate Cancer-Associated Human Retrovirus XMRV Lacks Direct Transforming Activity but Can Induce Low Rates of Transformation in Cultured Cells' Metzger M J (9 December 2009)
- 'Evolution of functional and sequence variants of the mammalian XPR1 receptor for mouse xenotropic gammaretroviruses and the human-derived XMRV' Y Yan et al. (J. Virology, 15 September 2010)
- 'Deciphering the Code for Retroviral Integration Target Site Selection' (PLoS Computational Biology, 24 November 2010)
- 'Contamination of clinical specimens with MLV-encoding nucleic acids: implications for XMRV and other candidate human retroviruses' Robert A Smith (Retrovirology, 20 December 2010)
- 'Disease-associated XMRV sequences are consistent with laboratory contamination' Hue (Retrovirology, 20 December 2010)
- 'Of mice and men: on the origin of XMRV' Van Der Kuyl (Frontiers in Virology, 26 December 2010)
- 'Crystal structure of XMRV protease differs from the structures of other retropepsins' Li (Nature Structural & Molecular Biology, 23 January 2011)
- 'NF-{kappa}B Activation Stimulates Transcription and Replication of Xenotropic Murine Leukemia Virus-Related Virus in Human B-lineage and Prostate Carcinoma Cells' Sakakibara (Journal of Virology, 26 January 2011)
- 'XMRV Protease Plasmid' (ATP, 13 January 2011)
- 'Severe Restriction of Xenotropic Murine Leukemia Virus-Related Virus Replication and Spread in Cultured Human Peripheral Blood Mononuclear Cells' Chaipan (Journal of Virology, 16 February 2011)
- 'Analysis of XMRV integration sites from human prostate cancer tissues suggests PCR contamination rather than genuine human infection' Garson (Retrovirology, 25 February 2011)
- 'XMRV infection induces host genes that regulate inflammation and cellular physiology' Lee (Journal of Urology, April 2011)
- 'Use of high throughput techniques in the identification of novel viral pathogens in acute and chronic diseases' Group Fischer (Universitätsklinikum Hamburg-Eppendorf, 24 March 2011)
- 'Implications for XMRV Infections in Prostate Cancer' Hong (Ohio Link, 2010)
- 'Gammaretroviral integration into nucleosomal target DNA in vivo' Roth (Journal of Virology, 11 May 2011)
- 'Testing Strategies for Detection of Xenotropic Murine Leukemia Virus Related Virus (XMRV) Infection' Tang (Hindawi, 15 May 2011)
- 'Identification of Replication Competent Murine Gammaretroviruses in Commonly Used Prostate Cancer Cell Lines' Sfanos (PLoSONE, 17 June 2011)
- 'Lack of Detection of Xenotropic Murine Leukemia Virus-Related Virus in HIV-1 Lymphoma Patients' Delviks-Frankenberry (Hindawi: Advances in Virology, 11 July 2011)
Assay development
- 'Rational recombinant XMRV antigen preparation and bead coupling for multiplex serology in a suspension array' Sheikholvaezin (Protein Expression and Purification, 19 August 2011)
Claimed origin of XMRV
- 'Of Mice and Men: On the Origin of XMRV' van der Kuyl (Frontiers in Virology, 17 January 2011)
- 'Recombinant Origin of the Retrovirus XMRV' Paprotka (Science, 31 May 2011) Video
- 'Recombinant Origin of the Retrovirus XMRV' - Supporting Online Material for Paprotka (Science, 31 May 2011)
- 'Xenotropic murine leukemia virus-related virus (XMRV) in prostate cancer cells likely represents a laboratory artifact' Yang (Impact journal, 2 June 2011)
- 'The left half of XMRV is present in an endogenous retrovirus of NIH/3T3 Swiss mouse cells' Mendoza (Journal of Virology, 22 June 20110
- 'Endogenous Murine Leukemia Viruses: Relationship to XMRV and MLVs Detected in Human DNA Samples' Coffin & Cingoz (Hindawi: Advances in Virology, 7 July 2011)
Contaminated equipment research studies
- 'An endogenous murine leukemia viral genome contaminant in a commercial RT-PCR Kit is amplified using standard primers for XMRV' Sato (Retrovirology, 20 December 2010)
- 'PCR Master Mixes Harbour Murine DNA Sequences. Caveat Emptor!' Tuke (PLoS ONE, 25 May 2011)
- 'DNA Extraction Columns Contaminated with Murine Sequences' Erlwein (PLoSONE, 18 August 2011)
Contaminated cell lines research studies
- 'Identification of Gammaretroviruses Constitutively Released from Cell Lines Used for Human Immunodeficiency Virus Research' Takeuchi, McClure, and Pizzato (Journal of Virology, December 2008)
Knox & Paprotka Editorials & updated official pages
- 'Editorial Expression of Concern' Bruce Alberts (Science, 31 May 201)
- 'XMRV and Human Disease Association: Questions and Answers' (NCI)
Reviews
- 'A new human retrovirus associated with prostate cancer' Fan (PNAS, 23 January 2007)
- 'Xenotropic Murine Leukemia Virus-Related Virus in Chronic Fatigue Syndrome and Prostate Cancer' James N. Baraniuk (Curr Allergy Asthma Rep., May 2010)
- 'The human retrovirus XMRV in prostate cancer and chronic fatigue syndrome' Silverman et al. (Nature Reviews Urology, July 2010)
- 'A cautionary tale of virus and disease' Robin A Weiss (BMC Biology, 27 September 2010)
- 'Current Status of Xenotropic Murine Leukemia Virus–Related Retrovirus in Chronic Fatigue Syndrome and Prostate Cancer: Reach for a Scorecard, Not a Prescription Pad' Mary Kearney and Frank Maldarelli (J Infect Dis., 11 October 2010)
- 'Detecting Retroviral Sequences in Chronic Fatigue Syndrome' Ila R. Singh (Viruses, 3 November 2010)
- 'Evidence and controversies on the role of XMRV in prostate cancer and chronic fatigue syndrome' Menéndez-Arias (Medical Virology, 26 November 2010)
- 'XMRV as a Human Pathogen?' Mark A. Wainberg & Kuan-Teh Jeang (Cell Host & Microbe, 21 April 2011) Full paper
- 'XMRV Discovery and Prostate Cancer Related Research' Kang (Advances in Virology, May 2011)
- 'Is XMRV a causal virus for prostate cancer?' Zhang (Asian Journal of Andrology, 18 July 2011)
- 'Origin of XMRV and its Demise as a Human Pathogen Associated with Chronic Fatigue Syndrome' Hohn & Bannert (Viruses, 27 July 2011)
Thesis on XMRV
- 'Evaluating XMRV As An Indicator Of Prostate Cancer Risk' Maria Barton (Ohiolink, July 2011)
Slides from unofficial talks
- Plenary Presentation at International workshop on HIV & Hepatitis virus: 'XMRV: Lessons learned from microbe hunters' John M. Coffin (Informed horizons: Tufts University, 7-11 June 2011)
Animal Studies
- 'XMRV: Examination of Viral Kinetics, Tissue Tropism, and Serological Markers of Infection' X Qiu et al. (CROI, 19 February 2010)
- 'Characterization of antibodies elicited by XMRV infection and development of immunoassays useful for epidemiologic studies' X Qui (Retrovirology, 17 August 2010)
- 'Organ and Cell Lineage Dissemination of XMRV in Rhesus Macaques during Acute and Chronic Infection' Sharma et al. (CROI, 19 February 2010)
- 'Common inbred strains of the laboratory mouse that are susceptible to infection by mouse xenotropic gammaretroviruses and the human derived XMRV' Baliji et al. (J Virology, 13 October 2010)
- 'Early Events in XMRV infection of wild-derived mouse, Mus pahari' Sakuma (J Virology, 17 November 2010)
- 'The mouse "xenotropic" gammaretroviruses and their XPR1 receptor' Kozak (Retrovirology, 30 November 2010)
- 'Infection, viral dissemination and antibody responses of Rhesus macaques exposed to the human gammaretrovirus XMRV' Onlamoon (Journal of Virology, 16 February 2011)
- 'Antibody Responses against Xenotropic Murine Leukemia Virus-Related Virus Envelope in a Murine Model' Makarova (PLoSOne, 6 April 2011) correction/patent for methods
- 'Sexual transmission of XMRV:a potential infection route' Sharma (Advances in Virology, 26 May 2011)
Relevant MLV research
- 'Human Immunodeficiency Virus Type 1 Genetic Recombination Is More Frequent Than That of Moloney Murine Leukemia Virus despite Similar Template Switching Rates' Onafuwa (Journal of Virology, April 2003)
- 'High Rate of Genetic Recombination in Murine Leukemia Virus: Implications for Influencing Proviral Ploidy' Zhuang (Journal of Virology, 12 April 2006)
- 'Endogenous retroviruses as potential hazards for vaccines' Takayuki Miyazawa (Biologicals, May 2010)
- 'Precise identification of endogenous proviruses of NFS/N mice participating in recombination with moloney ecotropic murine leukemia virus (MuLV) to generate polytropic MuLVs' Alamgir (Journal of Virology, April 2011)
- 'The mouse "xenotropic" gammaretroviruses and their XPR1 receptor' Christine A Kozak (Retrovirology, 30 November 2010)
- 'Sleep and fatigue in mice infected with murine gammaherpesvirus 68' Olivadoti (Science direct, 24 January 2011)
- 'Genome-wide analysis reveals novel molecular features of mouse recombination hotspots' Smagulova (Nature, 3 April 2011)
- 'The receptors for gibbon ape leukemia virus and amphotropic murine leukemia virus are not downregulated in productively infected cells' Liu (Retrovirology, 5 July 2011)
- 'Frequent detection of infectious xenotropic murine leukemia virus (XMLV) in human cultures established from mouse xenografts' Zhang (Landesbioscience, 1 October 2011)
- 'Naturally occurring polymorphisms of the mouse gammaretrovirus receptors CAT-1 and XPR1 alter virus tropism and pathogenicity' Kozal (Hindawi: Advances in Virology, 12 July 2011)
- 'Adaptive Introgression of Anticoagulant Rodent Poison Resistance by Hybridization between Old World Mice' Song (Current Biology, 21 July 2011)
- 'Murine Leukemia Viruses: Biology and Replication' Alan Rein (Hindawi: Advances in Virology, 27 July 2011)
Relevant HIV research
- 'Biology of HIV mucosal transmission.' Wu (Curr Opin HIV AIDS, September 2008)
Editorials on XMRV
- 'Mouse retroviruses and chronic fatigue syndrome: Does X (or P) mark the spot?' Courgnaud (PNAS, 23 August 2010)
Article on XMRV in journals
- 'XMRV and CFS—the sad end of a story' van Kuppeveld and van der Meer (The Lancet, 21 June 2011) full article
- 'Dangers of research into chronic fatigue syndrome' Nigel Hawkes (BMJ, 22 June 2011) Full article
- 'Commentary: Heading for a therapeutic stalemate' Trish Groves (BMJ, 22 June 2011) Full article
Government information on XMRV
- 'XMRV Protease Plasmid' PEL & NCI: Wlodawer, Esposito, Wall, Mehalko (Proteins and Proteomics, 27 April 2011)
- 'Origins of XMRV deciphered, undermining claims for a role in human disease' NIH (NIH, 2 June 2011)
- 'Perfect Match: Unraveling the Origin of XMRV' (NCI Cancer Bulletin, Volume 8 / Number 12, June 14, 2011 )
- 'Investigating Viruses in Cells Used to Make Vaccines; and Evaluating the Potential Threat Posed by Transmission of Viruses to Humans' FDA: Biologics research projects (FDA, update - July 2011)
1st International XMRV Conference
- Conference Website
- Conference Program
- Official Video of the conference Q&A, from the NIH
- 'Abstract Book: 1st international workshop on Xmrv' (Journal of abstracts and conference reports from international workshops on infectious diseases & antiviral therapy, Volume 8, 7-8 September 2010)
- Online PDF Presentations (7-8 September 2010)
- Abstracts from 1st International Workshop on XMRV
- 'The Xenotropic Murine Leukemia Virus-Related Retrovirus Debate Continues at First International Workshop' Stoye, Silverman, Boucher & Le Grice (CCROD, 17 December 2010) Also at Retrovirology
11th Symposium on Antiviral Drug Resistance
- 11th Symposium on Antiviral Drug Resistance: Program Book & abstracts (SADR, 7-10 November 2010.
Additional CFS Information
- 'Questions and Answer Session with: Dr. Judy Mikovits: Principal Investigator, Whittemore-Peterson Institute.' IACFS/ME (Newsletter, Volume 3, Issue 1 • April 2010)
- 'Inactivation of XMRV and MLV-related Viruses in Platelet and RBC Components Prepared with the INTERCEPT Blood System' Mikovits (1st XMRV Conference, 8 September 2010)
- Teleconference Q & A with authors of the PNAS study FDA (23 August 2010)
- 'FollowUp FAQs to the Study by Lo, Alter et al' CAA (Updated 6 September 2010)
- 'New study on the detection of murine leukemia virus-related virus gene sequences in the blood of patients with chronic fatigue syndrome (CFS) and healthy blood donors - Questions and Answers' FDA
- 'Infectious Disease and Cancer in Africa – A medical and Demographical Reality' Frimpong-Boateng (Keynote Lectures: “Global Health and Molecular Medicine I”, 3 November 2010)
Demystifying Medicine - Lo & Alter NIH 22 Feb 2011 Videocast
- VIDEO: 'Demystifying Medicine - Chronic Fatigue Syndrome: Is there a virus?' Gill, Lo, Alter (NIH, 22 February)
- VIDEOCAST: Demystifying Medicine - Chronic Fatigue Syndrome: Is there a virus? Lo & Alter (NIH, 22 February)
- SLIDES: Lo Lo (NIH, 22 February)
- SLIDES: Alter Alter (NIH, 22 February)
- SLIDES: Gill Gill (NIH, 22 February)
- 'Training Day' Charlotte von Salis (CFS Central, 24 February 2011)
CROI 2011
- Webcast Sessions (CROI 2011, 27 February to 2 March 2011)
- Podium video and slides: 'XMRV Probably Originated through Recombination between 2 Endogenous Murine Retroviruses during in vivo Passage of a Human Prostate Cancer Xenograft' Pathak (CROI 2011, 1hr 49mins, 2 March 2011)
- Podium video and slides: 'Themed Discussion: XMRV: New Findings and Controversies' (CROI 2011, 2 March 2011)
- ABSTRACT: 'XMRV Probably Originated through Recombination between 2 Endogenous Murine Retroviruses during in vivo Passage of a Human Prostate Cancer Xenograft' Paprotka (CROI, 2 March 2011)
- ABSTRACT: 'Development of a GFP-indicator Cell Line for the Detection of XMRV' Lee (CROI, 2 March 2011)
- ABSTRACT: 'XMRV Induces a Nonproductive Infection in Human Lymphoid Tissue' Curriu (CROI, 2 March 2011)
- ABSTRACT: 'Presence of XMRV Sequences in B Cells Are Restricted by APOBEC' Carrillo (CROI, 2 March 2011)
- ABSTRACT: 'Single Copy and Single Genome Sequencing Assays to Detect XMRV in Human Blood Products' Kearney (CROI, 2 March 2011)
- ABSTRACT: 'Discordant XMRV Test Results and Non-reproducible Mouse Endogenous Retroviral Detection in an XMRV Prevalence Study' Henrich (CROI, 2 March 2011)
- ABSTRACT: 'Extensive Genetic Recombination in the XMRV Genome' Switzer (CROI, 2 March 2011)
- ABSTRACT: 'Disease-associated XMRV Sequences Explained by Laboratory Contamination' Hué (CROI, 2 March 2011)
- ABSTRACT: 'Identification of a Novel Endogenous Murine Leukemia Virus as an XMRV Ancestor' Cingoz & Coffin (CROI, 2 March 2011)
- 'Determination of Host Range and Cellular Tropism of XMRV' Devadas (CROI, 1 March 2011)
- 'On the Origins of XMRV' Vernon (CAA, 4 March 2011)
Pathogens in the Blood Supply 2011
- ABSTRACTS: 'Disease Associations of XMRV and MLV-Related Viruses' Mikovits (NYAS, 29 March 2011)
15 International Conference on Human Retroviruses: HTLV and Related Viruses (June 2011)
- 'XMRV replicates preferentially in mucosal sites in vivo: Relevance to XMRV transmission?' Villinger (Retrovirology, 6 June 2011)
- 'Multi-laboratory evaluations of XMRV nucleic acid detection assays' Simmons (Retrovirology, 6 June 2011)
- 'Restricted infection of xenotropic murine leukemia virus-related virus in human lymphoid tissue' Curriu (Retrovirology, 6 June 2011)
- 'Human infection or lab artifact: will the real XMRV please stand up?' Silverman (Retrovirology, 6 June 2011)
- 'XMRV infection in human diseases' Erlwein (Retrovirology, 6 June 2011)
- 'In vitro assembly of xenotropic murine leukemia virus-related virus CA-NC protein' Hadravová (Retrovirology, 6 June 2011)
- 'Murine leukemia viruses (MuLV) and Xenotropic MuLV-related viruses exhibit inter-tropic complex recombination patterns' Prosperi (Retrovirology, 6 June 2011)
- 'Detection of MLV-like gag sequences in blood samples from a New York state CFS cohort' Hanson (Retrovirology, 6 June 2011)
- 'Serologic and PCR testing of persons with chronic fatigue syndrome in the United States shows no association with xenotropic or polytropic murine leukemia virus-related virus' Switzer (Retrovirology, 6 June 2011)
- 'Development of XMRV producing B Cell lines from lymphomas from patients with Chronic Fatigue Syndrome' Ruscetti (Retrovirology, 6 June 2011)
- 'Structure of the xenotropic murine leukaemia virus-related virus matrix protein' Dole¿al (Retrovirology, 6 June 2011)
- 'Independent evolution of intracellular transposons from exogenous IAP-related retroviruses in a broad range of mammalian species' Magiorkinis (Retrovirology, 6 June 2011)
- 'Cell line tropism and replication of XMRV' Devadas (Retrovirology, 6 June 2011)
- 'XMRV: usage of receptors and potential co-receptors' Setty (Retrovirology, 6 June 2011)
- 'The effects of XMRV gene expression on the mouse prostate' Rauch (Retrovirology, 6 June 2011)
- 'Prevalence of XMRV in blood donors, HTLV and HIV cohorts' Qiu (Retrovirology, 6 June 2011)
- 'Immune correlates of XMRV infection' Lombardi (Retrovirology, 6 June 2011)
- 'A prototype RT-PCR assay for detection of XMRV in multiple human sample types' Tang (Retrovirology, 6 June 2011)
- 'Heme oxygenase-1 activation inhibits XMRV pathogenesis and carcinogenesis in prostate cancer cells' Dhawan (Retrovirology, 6 June 2011)
- 'Exacerbated signs of an immunosuppressive AIDS-like disease in macaques infected with multiple retroviruses' Mitchell (Retrovirology, 6 June 2011)
- ABSTRACTS BOOK: '15th International Conference on Human Retroviruses: HTLV and Related Viruses' (Retrovirology, 6 June 2011)
Patents
- '(WO/2010/132886) COMPOSITIONS AND METHODS RELATING TO XMRV-RELATED DISEASES AND CONDITIONS' Ila Singh (WIPO, 18 November 2010)
- '(WO/2010/148323) DIAGNOSIS AND TREATMENT OF DISEASES OR DISORDERS ASSOCIATED WITH XENOTROPIC MURINE LEUKEMIA VIRUS' WPI (Wipo, 23 December 2010)
- '(WO/2011/041350) XENOTROPIC MULV-RELATED VIRUS (XMRV) COMPOSITIONS AND METHODS OF USE' Emory (Wipo, 7 April 2011)
- '(WO/2011/041512) COMPOSITIONS AND METHODS FOR TREATING MLV-INFECTION, AND PREVENTING AND TREATING MLV-INITIATED DISEASES' Emory (Wipo, 7 April 2011)
- '(WO/2011/002931) MARKERS OF XMRV INFECTION AND USES THEREOF' Abbott Labs (Wipo, 1 June 2011)
- 'DETECTION OF XENOTROPIC MURINE LEUKEMIA VIRUS' WPI: Mikovits, Lombardi, Ruscetti S, Ruscetti F, Silverman (USPTO, 23 June 2011)
- 'ANTIBODIES FOR DIAGNOSIS AND THERAPEUTIC TREATMENT OF PROSTATE CANCER' Kohli (freepatentsonline. 25 August 2011)
- '(WO2011092199) MUTATED XMRV ENV PROTEINS IN THE IMMUNOSUPPRESSIVE DOMAIN' INSTITUT GUSTAVE ROUSSY (Wipo, 4 August 2011)
Ampligen
- 'XMRV & AMPLIGEN: A Report from the 9th Hemispherx Biopharma Investigators Meeting March 3-6, 2011' Hunter-Hopkins ME-letter (Dr Lapp, 20 March 2011)
Blood donation & Blood XMRV Working Group
- 'National Expert Panel on New and Emerging Infections Meeting of Subgroup on Xenotropic Murine Leukaemia Virus-Related Virus (XMRV)' (DoH, 7 May 2010)
- XMRV Fact Sheet, AABB.org (formerly American Association of Blood Banks) USA, updated 18 June 2010
- 'Canadian Blood Services Responds To Possible New Blood Safety Threat' Canadian blood services (7 April 2010)
- 'Detailed Eligibility Criteria and FAQ's' NZ Blood Service (April 2010)
- 'Blood service updates CFS donor policy' Australian Blood Service (23 April 2010)
- 'Recommendation on Chronic Fatigue Syndrome and Blood Donation' AABB Interorganizational Task Force on XMRV, USA (18 June 2010)
- Association Bulletin #10-03 - Chronic Fatigue Syndrome and Blood Donation AABB (HHS, 18 June 2010)
- 'NATIONAL EXPERT PANEL ON NEW AND EMERGING INFECTIONS Minutes of the Thirteenth Meeting' (DoH, 21 June 2010)
- 'BLOOD PRODUCTS ADVISORY COMMITTEE' FDA (26 July 2010)
- 'Chronic fatigue syndrome sufferers cannot donate blood' National Blood Transfusion Services, Malta (4 September 2010)
- 'ME/CFS and blood donation: ME Association writes to the Acting Chief Medical Officer' MEA (15 August 2010)
- 'People with ME/CFS to be permanently excluded from giving blood in the UK from 1 November this year - Department of Health announcement' MEA (27 August 2010)
- 'American Red Cross Statement on XMRV and Chronic Fatigue Syndrome' (American Red Cross, 3 December 2010)
- 'Prohibition of ME sufferers to give blood in Norway from 10.12.2010' (10 December 2010)
- 'Statement Before the Blood Products Advisory Committee: Murine Leukemia Virus (MLV) Related Retroviruses and Blood Safety' Klein (AABB, 14 December 2010)
- SLIDES: 'Update of Blood XMRV Working Group Activities' Blood Products Advisory Committee (CAA, 14 December 2010)
- 'December 14, 2010: Blood Products Advisory Committee Meeting Transcript' (FDA, 14 December 2010)
- 'Xenotropic murine leukemia virus–related virus (XMRV) and blood transfusion: report of the AABB interorganizational XMRV task force' Klein (Transfusion, 14 January 2011)
- 'AABB Statement on XMRV' (AABB, 10 February 2011)
- 'What is XMRV and should we be worried about it?' Shan (Transfusion, 9 March 2011)
- 'Chronic Fatigue Syndrome. I have / have had Chronic Fatigue Syndrome.Can I give blood?' Irish Blood Tranfusion Service (Give Blood, 9 August 2011)
- 'Blood donation – statement by the Irish Blood Transfusion Service' Irish Blood Tranfusion Service (MEA, 14 April 2011)
- 'Xenotropic Murine Leukemia Virus-Related Virus (XMRV) and other Murine Leukemia Virus-Related Viruses (MLRV)' AABB (AABB, 2 May 2011)
- 'XMRV, Q fever and other emerging infections: impact on management of blood safety' Dodd (ISBT Science Series, 13 May 2011)
XMRV Resources
- Video: 'XMRV and Human Diseases' Ila Singh (OFFER Conference, 11 September 2010)
- University of Utah: XMRV
- Informational Presentation on XMRV, with list of research studies (FDA, 14 July 2010)
- 'TABLE: Prevalence Studies on XMRV and MLV-related Virus Infection in Human Diseases and General Populations' (FDA, 3 November 2010) [221]
- TIMELINE: 'A short history of XMRV' (WSJ, 5 March 2011)
- Retrovirus testing methodologies
CDC (USA)
- 'XMRV (Xenotropic Murine Leukemia Virus-related Virus)' (CDC, 23 August 2010)
- 'List of programs - Infectious Disease - Synthesis of XMRV Peptides' (CDC Foundation, checked on 25 January 2011)
HPA, DoH (UK)
- 'National Expert Panel on New and Emerging Infections Meeting of Subgroup on Xenotropic Murine Leukaemia Virus-Related Virus (XMRV)' (DoH, 7 May 2010)
- 'NATIONAL EXPERT PANEL ON NEW AND EMERGING INFECTIONS Minutes of the Thirteenth Meeting' (DoH, 21 June 2010)
- 'Infectious Disease Surveillance and Monitoring System for Animal and Human Health Summary of notable events/incidents of public health significance for the period 1st – 31st December 2010' (HPA, 7 January 2011)
- SLIDES: 'Update on XMRV in the U.S.' Indira K. Hewlett, Ph.D Chief, Laboratory of Molecular Virology DETTD/CBER/FDA XXII SoGAT meeting (NIBSC, 14/15 April 2011) SoGAT website
European Centre for disease prevention and control (ECDC)
- 'TECHNICAL REPORT: Risk assessment of XMRV - implications for blood donation' Tobias Bergroth, Mika Salminen, Ana-Belen Escriva. (STKB, 6 July 2011)
WPI & CAA on the XMRV Studies
- 'Official Statement from the Whittemore Peterson Institute Regarding UK Study' Frankie Vigil (WPI, 6 January 2010)
- 'XMRV Negative Results Emphasize Need for Robust Replication Study' Vernon (CAA, 6 January 2010)
- 'WPI is aware of the recent UK study that was unable to detect the presence of XMRV in any CFS patient samples.' (WPI, 18 February 2010)
- 'Second XMRV Negative Study … Still In Search of a Proper and Robust Replication Study' Vernon (CAA, 16 February 2010)
- 'Playing A Weak Hand Well' Vernon (CAA, 26 February 2010)
- 'Blood from a Stone' Suzanne D. Vernon (CAA, 1 July 2010)
- 'Whittemore Peterson Institute Statement regarding Centers for Disease Control XMRV Study' (WPI, 2 July 2010)
- 'Statement on XMRV/Chronic Fatigue Syndrome Positive replication study confirms WPI’s findings' (WPI, 23 August 2010)
- 'Of Mice and Men: A Summary of the First International XMRV Workshop' CAA (24 September 2010)
- 'Studies of the Prevalence of Evidence of Murine Leukemia Virus(es) in Patients with CFS 1st International XMRV Workshop: Oral and Poster Presentations' CAA (24 September 2010)
- 'WPI statement on XMRV research and PCR contamination' (WPI, 20 December 2010)
- From the CEO’s Desk: 4 studies in Retrovirology, the BPAC meeting, the XMRV workshop review, & new PLoSOne negative study McCleary (28 December 2010)
- 'Turning Today’s Discoveries Into Tomorrow’s Cures' Annette Whittemore (WPI, 1 January 2011)
- 'Response to Nature article regarding Dr Peterson' WPI (WPI, 28 March 2011)
- 'THE ITERATION OF X: Journal of Virology Study Finds No XMRV' Vernon (CAA, 5 May 2011)
- 'WPI response to the recent study' - Shin et al (WPI, 9 May 2011)
- 'Mikovits Response to the Editorial team of Science (WPI, 30 May 2011)
- 'WPI Response to the Science Editorial Expression of Concern' (WPI, 9 May 2011)
- 'New Science papers contribute more doubt to XMRV-CFS connection' CAA (Research 1st, 31 May 2011)
- 'XMRV: Trials and Tribulations' Vernon & McCleary (Research 1st, 1 June 2011)
- 'WPI Clinical Advisory Board response to Science' (WPI, 30 May 2011)
- 'Annette Whittemore's response to the Editor of Science' (WPI, 27 May 2011)
WPI/McClure Correspondance
- Letter to Dr. McClure from Annette Whittemore (WPI, 12 April 2010)
- Letter to Annette Whittemore/WPI from McClure (WPI, 2010)
- Letter to Dr. McClure from Annette Whittemore (WPI, 27 April 2010)
Van Kuppeveld/WPI Correspondence
- Letter to Annette Whittemore from Frank van Kuppeveld (UMC St Radboud, 22 April 2010)
Gerwyn
MRV Treatment
- 'Treatment Possibilities for the New Human Retroviruses' Mikovits (Gordon Medical, 17 January 2011)
Wall Street Journal
- 'So How Worried Are Public-Health Officials About XMRV?' Amy Dockser Marcus (WSJ, 7 April 2010)
- 'The AABB Makes it Official: CFS Patients Shouldn’t Give Blood' Amy Dockser Marcus (WSJ, 19 June 2010)
- 'Further Evidence of an XMRV-Chronic Fatigue Syndrome Connection?' Amy Dockser Marcus (WSJ, 23 June 2010)
- 'Chronic-Fatigue Link to Virus Disputed' Amy Dockser Marcus (WSJ, 30 June 2010)
- 'A.M. Vitals: Confusion Over XMRV-Chronic Fatigue Syndrome Continues' Katherine Hobson (WSJ, 30 June 2010)
- 'CDC Team’s XMRV-Chronic Fatigue Syndrome Paper Is Out' Amy Dockser Marcus (WSJ, 1 July 2010)
- 'Potential XMRV-Chronic Fatigue Syndrome Link Not Easy to Tease Out' Amy Dockser Marcus (WSJ, 15 July 2010)
- 'FDA Advisory Committee to Hear About XMRV Working Group’s Research' Amy Dockser Marcus (WSJ, 26 July 2010)
- 'Study Finds Retroviruses in Chronic Fatigue Sufferers' Amy Dockser Marcus (WSJ, 23 August 2010)
- 'PNAS Paper on Virus-Chronic Fatigue Syndrome Link Has Its Own Story' Amy Dockser Marcus(WSJ, 24 August 2010)
- 'Does X (the Virus, That Is) Mark the Spot in Chronic Fatigue Syndrome?' Amy Dockser Marcus (WSJ, 25 August 2010)
- 'Betting on X — As in XMRV — With a Big-Ticket Research Center' Amy Dockser Marcus (WSJ, 26 August 2010)
- '‘World Class Virus Hunter’ To Head Up the Latest XMRV Study' Amy Dockser Marcus (WSJ, 8 September 2010)
- 'XMRV On Everyone’s Mind at a Chronic Fatigue Syndrome Meeting' Amy Dockser Marcus (WSJ, 15 October 2010)
- 'What’s Next for X (as in XMRV)?' Amy Dockser Marcus (WSJ, 4 November 2010)
- 'Gearing Up for the Big Search for XMRV' Amy Dockser Marcus (WSJ, 17 November 2010)
- 'Seeking New Blood-Supply Test' Amy Dockser Marcus (WSJ, 23 November 2010)
- 'Abbott, Roche, Gen-Probe Among Those Seeking XMRV Test' Katherine Hobson (WSJ, 23 November 2010)
- XMRV: Red Cross Now Barring Blood Donors Who Have CFS' Amy Marcus Dockser (WSJ, 3 December 2010)
- 'New Blood-Screening Advised: Advisory Panel Says Victims of Chronic Fatigue Syndrome Be Barred From Donating' Amy Marcus Dockser (WSJ, 15 December 2010)
- 'How Common is it For Chronic-Fatigue Syndrome Patients to Give Blood?' Katherine Hobson (WSJ, 15 December 2010)
- 'XMRV: Still Waiting For a Test' Amy Marcus Dockser (WSJ, 17 December 2010)
- 'XMRV: How To Screen the Blood Supply' Amy Dockser Marcus (WSJ, 20 December 2010)
- 'XMRV: Raising the Issue of Contamination' Amy Dockser Marcus (WSJ, 20 December 2010)
- 'XMRV: Testing the Blood Supply' Amy Dockser Marcus (WSJ, 20 January 2011)
- 'XMRV: Study Shows Virus Can Cause ‘Persistent Infection’ in Monkeys' Amy Dockser Marcus (WSJ, 17 February 2011)
- 'The Puzzle of Chronic Fatigue' Amy Dockser Marcus (WSJ, 5 March 2011)
- VIDEO: 'Rural NY Town Becomes Chronic Fatigue Laboratory' Jason Bellini (WSJ, 4 March 2011)
- 'XMRV and the Blood Supply: More Study Needed' Amy Dockser Marcus (WSJ, 7 March 2011)
- 'Amid War on a Mystery Disease, Patients Clash With Scientists' Amy Dockser Marcus (WSJ, 12 March 2011)
- 'A.M. Vitals: Chronic Fatigue Syndrome Patients, Researchers Clash' Katherine Hobson (WSJ, 14 March 2011)
- 'Unlocking Chronic Fatigue Syndrome' Amy Dockser Marcus (WSJ, 22 March 2011)
- 'At NIH Chronic Fatigue Syndrome Conference, XMRV Debate Heats Up' Amy Dockser Marcus (WSJ, 8 April 2011)
- 'Study Finds No Link Between XMRV and Chronic Fatigue Syndrome' Amy Dockser Marcus (WSJ, 4 May 2011)
- 'Chronic-Fatigue Paper Called Into Question' Amy Dockser Marcus (WSJ, 31 May 2011)
- 'Science Papers ‘Cast Further Doubt’ on XMRV’s Link to Chronic Fatigue Syndrome' Amy Dockser Marcus (WSJ, 31 May 2011)
- 'Given Doubt Cast on CFS-XMRV Link, What About Related Research?' Amy Dockser Marcus (WSJ, 1 June 2011)
Further News Coverage
- 'Virus linked to prostate tumours' (BBC, 7 September 2010)
- 'Our Vietnam War ended today' Hillary Johnson (Osler's Web, 8 October 2009)
- 'Virus Is Found in Many With Chronic Fatigue Syndrome' Denise Grady (NYT, 8 October 2009)
- 'Virus linked to chronic fatigue syndrome' Lizzie Buchen (Nature news, 8 October 2009)
- 'Is a Virus the Cause of Fatigue Syndrome?' Denise Grady (NYT, 12 October 2009)
- 'A Case of Chronic Denial' Hillary Johnson (NYT, 20 October 2009)
- 'Bill Reeves: The Decider' Hillary Johnson (Osler's Web, 24 October 2009)
- 'Fibromyalgia, H.I.V. and Chronic Fatigue' Q & A Dr. Klimas (NYT, 21 January 2010)
- 'A handpuppet bites the dust: A chronicle in eight parts' Hillary Johnson (Osler's Web, 3 April 2010)
- 'Virus leads Canadian Blood Services to ban certain donors' Joseph Hall (Hamilton Spectator, 6 Apr 2010)
- 'Virus leads Canadian blood service to ban certain donors' Joseph Hall (Healthzone Ca, 6 April 2010)
- 'No blood from chronic fatigue donors: agency' CBS, Canada (7 April 2010)
- 'O Canada' Hillary Johnson (Osler's Web, 7 April 2010)
- 'Chronic Fatigue Set To Disqualify Blood Donors' Kent Atkinson (NZPA, NZ, 21 April 2010)
- 'Positieve ‘XMRV-studie’ kwestie van tijd' (Voedinge, 3 May 2010) TranslationTranslation
- 'Going Viral' Brian Vastag (Cleveland Clinic, Summer 2010)
- 'Original Press Release from the Netherlands: FDA and NIH confirm 'XMRV findings' MMD Newswire (Netherlands, 22 June 2010)
- 'The Big One' Hillary Johnson (Osler's Web, 22 June 2010)
- 'Rubber Meets Road' Hillary Johnson (Osler's Web, 30 June 2010)
- 'Chronic fatigue findings were held back' Heidi Ledford (Nature, 2 July 2010)
- 'Study that 'solves' chronic fatigue syndrome blocked' Steve Connor (The Independent, 9 July 2010)
- 'Findings by Reno scientists confirmed by U.S. government' Lenita Powers (Reno Gazette Journal, 16 August 2010)
- 'Study: Presence of Murine Leukemia Virus Related Gene Sequences Found in CFS Patients' PR Newswire (23 August 2010)
- 'Q&A: Why I delayed XMRV paper' Cristina Luiggi (The Scientist, 23 August 2010)
- 'New evidence that virus may cause chronic fatigue' Rob Stein (The Washington Post, 23 August 2010)
- 'Chronic Fatigue Linked to Virus Class' David Tuller (NYT, 23 August 2010)
- 'Mouse virus link to chronic fatigue is studied' Associated Press (Forbes, 23 August 2010)
- 'Second Paper Supports Viral Link to Chronic Fatigue Syndrome' Martin Enserink (Science, 23 August 2010)
- 'New research linking chronic fatigue syndrome to retrovirus is released after being held by journal' Katherine Harmon (Scientific America, 23 August 2010)
- 'The FDA/NIH/Harvard “XMRV” study: The same thing, only different' Mindy Kitei (CFS Central, 23 August 2010)
- 'Fatigue chronique : la suspicion s'accroît autour d'un virus' Stéphane Foucart (Le Monde, 3 September 2010)
- 'XMRV Conference Recap' Mindy Kitei (CFS Central, 13 September 2010)
- 'Answers Being Found on CFIDS and Fibromyalgia- What Benefits for Ill Gulf War Veterans?' Denise Nichols (Veterans Today, 15 September 2010)
- 'Dr. Paul Cheney's Poster Presentation' Mindy Kitei (CFS Central, 16 September 2010)
- 'No Meeting of Minds on XMRV's Role in Chronic Fatigue, Cancer' Jocelyn Kaiser (Science, 17 September 2010)
- 'Chronic fatigue syndrome: going viral?' (The Lancet, 18 September 2010)
- "We thought we were almost done with XMRV..." Hillary Johnson (Oslers Web, 2 October 2010)
- 'Virus Linked to Chronic Fatigue Syndrome' NIH (NIH News in Health, October 2010)
- 'ME patients face UK ban on donating blood' Michelle Roberts (BBC, 8 October 2010)
- 'ME sufferers banned from giving blood' Nick Collins (Telegraph, 8 October 2010)
- 'ME patients banned from donating blood in UK following virus link fears' Daily Mail Reporter (Mail Online, 8 October 2010)
- 'Mystery Virus Still Keeping Secrets' Michael Smith (MedPage Today, 13 October 2010)
- 'Suzanne Vernon's take on two XMRV studies' Mindy Kitei (CFS Central, 15 November 2010)
- 'A Man From Whom Viruses Can’t Hide' Carl Zimmer (NYT, 22 November 2010)
- 'Validation In a Virus?' Claudia Kalb (Newsweek, 28 November 2010)
- 'Red Cross bars chronic fatigue patients from donating blood' Rob Stein (Washington Post, 3 December 2010)
- Advert in Washington Post MCWPA (Washington Post, Page A12, 6 December 2010)
- 'Chronic Fatigue Syndrome Patients Run First-ever Ad in The Washington Post' Coral Gables (PR Newswire, 6 December 2010)
- 'Chronic Fatigue Syndrome Patients Run First-ever Ad in The Washington Post' Coral Gables (Miami Herald, 6 December 2010)
- 'Patients with ME/CFS take it in their own hands' KatiforXMRV (ireport CNN, 7 December 2010)
- 'FDA advised to turn away blood donors with chronic fatigue syndrome' (Nature, 16 December 2010)
- 'The Big Sweat' Christopher Cairns (CFS Patient Advocate, 16 December 2010)
- PRESS RELEASE 'New UK study casts doubts on the link between XMRV and ME/CFS' Wellcombe Trust Sanger Institute (MEA, 20 December 2010)
- 'ME, or chronic fatigue syndrome, 'not caused by the XMRV virus', say researchers' Helen Briggs (BBC, 20 December 2010) - Previously called, 'ME 'not caused by the XMRV virus. [222]
- 'Prof. Kenny De Meirleirs uttalelse om de 5 publiserte kontaminerings-studiene' Rutts tankespinn (Merutt, 20 December 2010)
- 'The Mouse that Roared' Christopher Cairns (CFS Patient Advocate, 20 December 2010)
- 'Scientists conclude mouse virus does not cause ME' Sarah Boseley (Guardian, 20 December 2010)
- 'ME 'virus' was actually a lab mistake, study says' Steve Connor (Independent, 21 December 2010)
- 'Is XMRV a laboratory contaminant?' Vincent Racaniello (TWiV, 21 December 2010)
- 'New challenge to link between virus and chronic fatigue syndrome' Heidi Ledford (Nature, 21 December 2010)
- 'Contamination May Have Marred XMRV Studies' John Gever (Medpage Today, 21 December 2010)
- 'Chronic fatigue syndrome 'not virus (NHS Choices, 21 December 2010) - Title changed to 'Chronic fatigue syndrome virus doubt' on the 22 December 2010.
- 'Annette Whittemore and Judy Mikovits Nevada Newsmakers' Nevada Newsmakers (YouTube, 21 December 2010)
- 'Transcription of Sam Shad's interview with Annette Whittemore and Dr Mikovits on Retro-contamination papers' Nevada Newsmakers (XMRV Global Action, 21 December 2010)
- 'XMRV and CFS – It’s not the end' Vincent Racaniello (TWiV, 22 December 2010)
- 'Fahrenheit 451 for what ails you' Joel Spinhirne (Daily Kos, 22 December 2010)
- 'Biomedical Research into ME: Proper Science Will Prevail' Invest in ME (Invest in ME, 23 December 2010)
- 'Chronic fatigue syndrome is not caused by XMRV virus, study shows' Jo Carlowe (BMJ, 23 December 2010)
- 'Dr. Coffin Responds' Mindy Kitei (CFS Central, 23 December 2010)
- 'Exhausted by Illness, and Doubts' David Tuller (NYT, 3 January 2011)
- 'The Lingering Mystery of Chronic Fatigue Syndrome' Toby Bilanow (NYT, 3 January 2011)
- 'David Tuller, NY Times, on XMRV' Christopher Cairns (CFS Patient Advocate, 4 January 2011)
- 'Macaque monkeys and XMRV' CFIDS Watch (CFIDS Watch, 6 January 2011)
- 'Studies Point to Possible Contamination in XMRV Findings' Jocelyn Kaiser (Science, 7 January 2011)
- 'Full Interview: Dr. Eric Klein of the Cleveland Clinic Talks about XMRV Research' Craig Maupin (The CFS Report, 7 January 2011)
- 'UPDATE - Wellcome Trust Researchers Respond to Criticism of Their XMRV Virus Conclusions' (Scicasts, 13 January 2011)
- 'PART 1: 1/17/11 XMRV presentation by Dr. Judy Mikovits and Annette Whittemore' (Lannie in the lymelight, 17 January 2011)
- 'PART 2: 1/17/11 XMRV presentation by Dr. Judy Mikovits and Annette Whittemore' (Lannie in the lymelight, 19 January 2011)
- 'Barbara Baumgarten-Austrheim deler mer informasjon om XMRV-testingen på Oslo Universitetssykehus' Skrevet av Rutt (Rutts tankespinn og ME-nyheter, 16 February 2011) 'Translations'
- 'XMRV infection of Rhesus macaques' Vincent Racaniello (Virology blog, 17 February 2011)
- 'Walking on eggshells: PCR assays for XMRV detection' Andrew S. Wiecek (BioTechniques.com, 23 February 2011)
- 'Cover-up and contamination theories' Jaime Deckoff-Jones (TreatingXMRV, 6 March 2011)
- 'Fresh Doubts About Connection Between Mouse Virus and Human Disease' Jon Cohen (Science Now, 8 March 2011)
- 'The CROI insider' Mindy Kitei (CFS Central, 8 March 2011)
- 'More Negative Data for Link Between Mouse Virus and Human Disease' Jon Cohen (Science, 11March 2011)
- 'CD57: A Marker for ARVs?' Mindy Kitei (CFS Central, 11 March 2011)
- 'Vaccinations and Frankencells' Jamie Deckoff-Jones (TreatingXMRV, 13 March 2011)
- 'Virology: Fighting for a cause' Ewen Callaway (Nature news, 14 March 2011)
- 'A Theory of XMRV Creation' Kent Heckenlively (Age of Autism, 15 March 2011)
- 'British Invasion' Mindy Kitei (CFS Central, 16 March 2011)
- EDITORIAL: 'Cause for concern: Scientists studying diseases should be motivated by patients, but not led by them' (Nature, 16 March 2011)
- 'Mysterious Autism Virus(es) revealed?' Dr Jeff Bradstreet (Dr Jeff Bradstreet, 17 March 2011)
- 'Science fiction or science fact?' Jamie Deckoff-Jones (19 March 2011)
- 'Willard' Mindy Kitei (CFS Central, 19 March 2011)
- 'More on Dr. Judy Mikovits's New Role' Mindy Kitei (CFS Central, 24 March 2011)
- 'Reflections about right and wrong' Jamie Deckoff-Jones (X Rx, 27 March 2011)
- 'The vanishing' Mindy Kitei (CFS Central, 29 March 2011)
- 'Mouse viruses and human disease' Magiorkinis (The Lancet, April 2011)
- 'XMRV ou l’incroyable saga d’un virus' - 'XMRV and the incredible virus story' Stéphane Foucart (Le Monde, 2 April 2011)
- 'Chronic Fatigue Syndrome: Lives Interrupted' Llewellyn King (White House Chronicle, 4 April 2011)
- 'The Great Apologizer' Chris Cairns (Patient Advocate, 9 April 2011)
- 'You're it' Lilly Meehan (CFS Central, 10 April 2011)
- 'NIH State of Knowledge April 7-8, 2011' Chris Cairns (Patient Advocate, 12 April 2011)
- 'Q & A with CAA's Dr. Suzanne Vernon' Mindy Kitei (CFS Central, 13 April 2011)
- 'A Rose By Any Other Name' Jamie Deckoff-Jones MD (X Rx, 14 April 2011)
- 'Another Perspective' Jamie Deckoff-Jones (X Rx, 21 April 2011)
- 'Emerging retrovirus meets match in emerging retrovirologist' Alex Compton (University of Washington: The MCB transcript, 26 April 2011)
- 'Aloha' Jamie Deckoff-Jones (X Rx, 1 may 2011)
- 'Further comments from Dr. Snyderman' Dr. Snyderman (X Rx, 2 may 2011)
- 'Sick and tired' Michael Barrett (New Statesman, 5 May 2011)
- 'Ila Singh finds no XMRV in patients with chronic fatigue syndrome' Vincent Racaniello (Virology blog, 4 May 2011)
- 'Chronic Fatigue Syndrome Not Related to XMRV Retrovirus, Comprehensive Study Finds' (Science Daily, 4 May 2011)
- 'More questions over link between XMRV and chronic fatigue syndrome' Ewen Callaway (Nature news blog, 5 May 2011)
- 'More Bad News for Chronic Fatigue Syndrome and the Mouse Virus Thesis' Jon Cohen (Science: Insider, 6 May 2011)
- 'Dr. Ila Singh' Mindy Kitei (CFS Central, 6 May 2011)
- 'Ian Lipkin on XMRV' Vincent Racaniello (Virology blog, 6 May 2011)
- 'Blood versus tissue' Mindy Kitei (CFS Central, 7 May 2011)
- 'Вирус-призрак' Дарья Золотухина (Rusrep, 8 May 2011)
- 'The Shell Game' Jamie Deckoff-Jones (X Rx, 9 May 2011)
- 'Study Discounts Chronic Fatigue Link to Mouse Retrovirus' Michael Smith (Medpage Today, 9 May 2011)
- 'Have you no sense of decency?' Mindy Kitei (CFS Central, 11 May 2011)
- 'Judy Mikovits' new study' Mindy Kitei (CFS Central, 13 May 2011)
- 'Science raises questions about XMRV study' Ewen Callaway (Nature, 31 May 2011)
- Concern' over ME/viral research' James Gallagher (BBC, 31 May 2011)
- 'Science does the right thing, releasing XMRV-chronic fatigue material early, no sanctions for WSJ' (Embargowatch, 31 May 2011)
- 'The chronic fatigue virus: de-discovered?' Carl Zimmer (Discover Magazine, 31 May 2011)
- 'New Data Spark Retraction Request for Chronic Fatigue Virus Study' Jon Cohen (Science Now, 31 May 2011)
- 'Chronic Fatigue Study That Sparked Ban May Have Been Flawed' Elizabeth Lopatto and Michelle Fay Cortez (Bloomberg, 31 May 2011)
- 'Mouse virus doesn't cause chronic fatigue: reports' Julie Steenhuysen (Reuters, 31 May 2011)
- 'A Sad Day For Patients' Jamie Deckoff-Jones (X Rx, 31 May 2011)
- 'Origins of XMRV deciphered, undermining claims for a role in human disease' NIH (Medical Press, 31 May 2011)
- 'Retrovirus No Longer Thought to Be Cause of Chronic Fatigue Syndrome' Erica Westly (Scientific America, 1 June 2011)
- 'Flaws in Mouse Virus Link to Chronic Fatigue Syndrome Known Before Blood Ban, States Cooperative Diagnostics' Doug Pennock (Gamut News, 1 June 2011)
- '2 Studies Examine Syndrome of Fatigue' David Tuller (NYT, 1 June 2011)
- 'Mouse virus doesn't cause chronic fatigue syndrome' Andy Coghlan (New Scientist, 2 June 2011)
- 'STEVEN SALZBERG'S PSEUDOSCIENCE' Mindy Kitei (CFS Central, 2 June 2011)
- 'Chronic fatigue syndrome: life after XMRV' Ewen Callaway (Nature news, 3 June 2011)
- 'SAVE ME FROM STEVEN SALZBERG (Part 2)' Mindy Kitei (CFS Central, 3 June 2011)
- 'Moving forward in an imperfect world' Christopher Cairns (Patient Advocate, 3 June 2011)
- 'The Fire Smolders' Jamie Deckhoff-Jones (X Rx, 7 June 2011)
- 'Once more unto the breach, dear friends' Jamie Deckhoff-Jones (X Rx, 8 June 2011)
- 'Far from the clinic, Tufts virologists draw ire from some chronic fatigue syndrome patients' Tinker Ready (Nature: Boston blog, 10 June 2011)
- 'Whodunit?' Jamie Deckhoff-Jones (X Rx, 11 June 2011)
- 'DUSTY MILLER'S XMRV STUDY' Mindy Kitei (CFS Central, 14 June 2011)
- 'DUSTY MILLER REDUX - Second Email Exchange Between Dusty Miller and CFS Central' Mindy Kitei (CFS Central, 16 June 2011)
- 'Now doctors say M.E. is NOT caused by virus but is found in the blood' Sophie Borland (Mail online, 21 June 2011)
- 'ME 'not caused by virus', scientists announce' Andy Bloxham (The Telegraph, 21 June 2011)
- 'EDITORIAL: Too soon to translate?' EDITORIAL (Nature Medicine, 7 July 2011)
- 'Chronic Fatigue Syndrome Link to Retrovirus Likely the Result of Lab Contamination, Studies Find' Gina Shaw (Neurology Today, 7 July 2011)
- 'Prostate cancer: XMRV—contaminant, not cause?' Suzanne J. Farley (Nature Reviews: Urology, 14 July 2011)
- 'Animal testing 'requires tighter regulation' James Gallagher (BBC, 22 July 2011)
- 'Human, animal DNA mixing needs oversight' (CBS, 22 July 2011)
- 'Squeaks and Peeps - and a few sharp bites' Chris Cairns (CFS Patient Advocate, 3 August 2011)
Press Release from Wellcome Trust
- 'Chronic Fatigue Syndrome is not caused by XMRV' Wellcome Trust (Wellcome Trust Sanger Institute, 20 December 2010)
- 'Chronic fatigue syndrome not caused by XMRV virus, study shows' Wellcome Trust (Wellcome Trust, 6 January 2011)
Press Release from University of Utah
- 'Chronic Fatigue Syndrome Is Not Related to XMRV Retrovirus, Comprehensive Study Finds' Phil Sahm (Utah, 4 May 2011)
