Author Topic: Role of natural pseudotyping with other viruses in HIV transmission  (Read 1003 times)

jemal

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I have been on a 2 week hiatus, so I am not sure if this was already posted (I missed a lot and it's hard to catch up). This is a new project that popped up in the NIH database, it got over $700.000.

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Project Start Date: 30-SEP-2011
 Project End Date: 31-JUL-2016

The global AIDS pandemic continues to expand despite significant advances in understanding HIV-1 pathogenesis and the development of powerful antiviral drugs. HIV-1 is transmitted primarily through sexual contact and more than 30 million people are currently infected worldwide. In some regions of the world such as southern Africa the prevalence of HIV-1 infection exceeds 20%. The devastating spread of HIV-1 in young women in these countries appears out of proportion to the overall risk of infection. Thus it is possible that a biological co-factor contributes to virus spread. The hypothesis of this proposal is that acquisition by HIV- 1 of the envelope glycoprotein of gammaretroviruses (murine leukemia virus-related viruses) in a process we call ""natural pseudotyping"" expands the cellular tropism of HIV-1 enabling it to directly infect vaginal epithelial cells thereby dramatically increasing the risk of infection during sexual intercourse. We propose a molecular epidemiology study consisting of four major aims. 1) To complete in vitro studies of gammaretrovirus/HIV-1 pseudotyping; 2) To demonstrate gammaretrovirus/HIV-1 co-infections in local donors; 3) To demonstrate the effect of gammaretrovirus pseudotyping on vaginal transmission in an animal model; 4) To determine the prevalence of gammaretrovirus infection and HIV-1 co-infection in southern Africa. Natural pseudotyping of HIV-1 is predicted to occur in individuals co-infected with HIV-1 and a gammaretrovirus (xmrv/MLV) since the cellular tropism of these two viruses overlap to include T cells. The formation of xmrv-pseudoptyped HIV-1 (HIV-1/gp70) (now with the cell tropism of xmrv) in blood or lymphoid tissue would result in HIV-1 infection of normally resistant cells in the urogenital tract. Prior or subsequent infection of these cells with xmrv would result in the release of HIV-1/gp70 into seminal fluid or vaginal secretions. The potential implications of natural pseudotyping of HIV-1 are profound.

http://projectreporter.nih.gov/project_info_description.cfm?aid=8144150&icde=10094017

B8b_E

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Re: Role of natural pseudotyping with other viruses in HIV transmission
« Reply #1 on: October 13, 2011, 09:36:56 PM »
Probably the 'risk of sexual intercourse' for someone with severe ME is quite low, or in my case a once in a life time event.

Interesting to know though, for people who are more 'active'.

Maybe we're infectious only for the first few weeks, before virus migrates to tissue and if you feel really Flu Like you'd probably not be romancing someone during this time when you think you 'cath' a really bad Flu.

Who knows.  :(
« Last Edit: October 13, 2011, 09:45:08 PM by B8b_E »

Dr. Yes

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Re: Role of natural pseudotyping with other viruses in HIV transmission
« Reply #2 on: October 13, 2011, 11:09:28 PM »

Very interesting.  Thanks Jemal!

I hope this scientist doesn't merely look for XMRV (a la Silverman) envelope, however.  That's the one thing the WPI and NCI could not find by PCR, and the envelope fragments they have sequenced are distinct from Silverman XMRV.
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Tango

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Re: Role of natural pseudotyping with other viruses in HIV transmission
« Reply #3 on: October 13, 2011, 11:16:38 PM »
HIV deadly 99% + HGRVs aerosolised =  :o
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Superjump

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Re: Role of natural pseudotyping with other viruses in HIV transmission
« Reply #4 on: October 13, 2011, 11:20:28 PM »
Probably the 'risk of sexual intercourse' for someone with severe ME is quite low, or in my case a once in a life time event.

Interesting to know though, for people who are more 'active'.

Maybe we're infectious only for the first few weeks, before virus migrates to tissue and if you feel really Flu Like you'd probably not be romancing someone during this time when you think you 'cath' a really bad Flu.

Who knows.  :(

Yeah, even if the slim and none offers to exercise my 'downstairs giggle place' increased by one, and I was well enough to do something about it, the guilt attached to the risks kinda cancels it back out.

jemal

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Re: Role of natural pseudotyping with other viruses in HIV transmission
« Reply #5 on: October 14, 2011, 07:53:03 PM »
This study is led by James Hildreth. I did some Googling and he is not new to XMRV. Dr. Mikovits and him have apparently been in contact as well (at least in the past). Some background information from a XMRV seminar in 2010:
 
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Question: Because I’m wondering, I’ve met a lot of other CFS patients who like me have high cholesterol. That just made me think: might there be a correlation?

Dr. Mikovits:  Yeah, and nobody’s ever looked. It’s certainly something that they could look at correlating. I can’t think of a reason why. You might presume you’d have less, if you’re using it up for another purpose.

Question: What about children?

Dr. Mikovits:  We do have a little bit of data on that because we have two children in a study who have a genetic disease of cholesterol.  It’s called Niemann-Pick’s Disease. It’s also known as Childhood Alzheimer’s. And these kids, you know it’s a cholesterol metabolism disease where eventually your brain, you’ll eventually die of it because if you get too much cholesterol, it messes up your brain and everything. And those kids have been treated by James Hildreth in Nashville, Tennessee, at a small college...  He’s using Cyclodextran and some of the cholesterol drugs.  He’s actually an HIV drug developer, and the kids are showing some improvement when he modulates that pathway and stops the virus from entering or exiting the cell, so we don’t know anything about XMRV.  We just know what other viruses do, so he is having success, suggesting that there are some opportunities there.

Question: Are you working with him?

Dr. Mikovits:  Yeah, we’re working with him as well. That’s why I didn't list all the collaborators in the United States. We’re providing reagents and whatever intellectual knowledge we have, and whatever physical abilities and instruments we have, to these collaborative efforts as well.

http://www.prohealth.com/library/showarticle.cfm?libid=15173

This study also uses cells from James Hildreth:
XMRV accelerates cellular proliferation, transformational activity, and invasiveness of prostate cancer cells by downregulating p27Kip1

http://onlinelibrary.wiley.com/doi/10.1002/pros.21491/full

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Once infected, LNCaP cells produce XMRV continuously. We use chronically infected LNCaP cells with XMRV (a gift from Dr. James Hildreth [...])
« Last Edit: October 14, 2011, 07:59:08 PM by jemal »

B8b_E

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Re: Role of natural pseudotyping with other viruses in HIV transmission
« Reply #6 on: October 14, 2011, 07:59:09 PM »
HIV deadly 99% + HGRVs aerosolised =  :o

Probably that would lead to a situation you'd need to get the military to cover up with an extremist army psychiatrist who gets sole funding into a 'fatigue' syndrome
hiding the original HGRV accident.


Tango

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Re: Role of natural pseudotyping with other viruses in HIV transmission
« Reply #7 on: October 14, 2011, 10:49:31 PM »
What an imagination!  Really where have you been hanging out?

Anyone would think you had been talking  to a bunch of AIDS patients from the 80s using a Ouija board.
"I suspect there have been a number of conspiracies that never were described or leaked out. But I suspect none of the magnitude and sweep of Watergate." Woodward

"I would favor any name that does not impose (or give the appearance of imposing) taxonomic preconceptions on the nomenclature." Coffin

Val

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Re: Role of natural pseudotyping with other viruses in HIV transmission
« Reply #8 on: October 14, 2011, 11:50:54 PM »
I noticed the funding comes from the Office of the Director, National Institutes of Health. 


So, it's not from any of the individual institutes, such as NIAID.  Does the Office of Women's Health reside in the Director's office?


Is a NICE chunk of $$.  That's good to see.

noddy

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Re: Role of natural pseudotyping with other viruses in HIV transmission
« Reply #9 on: October 15, 2011, 12:04:20 AM »
Yeah, even if the slim and none offers to exercise my 'downstairs giggle place' increased by one, and I was well enough to do something about it, the guilt attached to the risks kinda cancels it back out.

big big LOL at 'downstairs giggle place'.
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Superjump

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Re: Role of natural pseudotyping with other viruses in HIV transmission
« Reply #10 on: October 15, 2011, 08:26:00 PM »
big big LOL at 'downstairs giggle place'.

Lovingly pilfered from Blamimation 7 : http://penny-arcade.com/patv/episode/blam-7  ;D (Caution, explicit lyrics!)