Role of natural pseudotyping with other viruses in HIV transmission

[Jemal]

For those who want to remove the XMRV section on this forum, this story is not over yet. This is a new project that the NIH just funded with almost $800.000. Clearly some people are still interested in the possibility gammaretroviruses are infecting humans.

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

edit: I tried to catch up with all the threads and I think this hasn't been posted yet. If it was, sorry!

 

[currer]

This explains all the studies previously published looking for XMRV in HIV patients.

I wondered at the time why they were focusing so much on looking for XMRV in HIV positive people, when we know that most ME patients are female and not at high risk of HIV infection.

They were checking for pseudotyping - HIV inserting its genome into a gammaretrovirus envelope.

But they didnt say so, did they?

 

[RustyJ]

WOW! Good pick up Jemal.

The potential implications of natural pseudotyping of HIV-1 are profound

Not to mention the implications for MLV infection.

To demonstrate gammaretrovirus/HIV-1 co-infections in local donors

This doesn't sound like a fishing expedition to me. Seems like they already know it's happening. I wonder if there has been a study published previously.

 

[Jemal]

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:

Question: Because Im wondering, Ive 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 nobodys ever looked. Its certainly something that they could look at correlating. I cant think of a reason why. You might presume youd have less, if youre 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. Its called Niemann-Picks Disease. Its also known as Childhood Alzheimers. And these kids, you know its a cholesterol metabolism disease where eventually your brain, youll 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... Hes using Cyclodextran and some of the cholesterol drugs. Hes 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 dont 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, were working with him as well. Thats why I didn't list all the collaborators in the United States. Were 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

 

[Forebearance]

Thanks for this, Jemal. This sounds important. It made me gasp while sitting in a Starbuck's, anyway.

 

[Bob]

2) To demonstrate gammaretrovirus/HIV-1 co-infections in local donors
...
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.

Interesting that it is a full investigation for XMRV. But I wonder what makes them think they will find XMRV, when so many others have failed.
There have been other studies looking at XMRV/HIV co-infections and they haven't found XMRV.

This explains all the studies previously published looking for XMRV in HIV patients.

I wondered at the time why they were focusing so much on looking for XMRV in HIV positive people, when we know that most ME patients are female and not at high risk of HIV infection.

They were checking for pseudotyping - HIV inserting its genome into a gammaretrovirus envelope.

But they didnt say so, did they?

I don't remember them saying so either currer.

I don't know anything about pseudotyping...

So I wonder if it is widespread in human viruses?

If they find that HIV can insert its genome into a gammaretrovirus, then would this open up research into other types of pseudotyping, I wonder?

Does HIV become a stealth virus if it acquires the envelope glycoprotein of gammaretroviruses? Or does the gammaretrovirus become a stealth virus?

Wasn't there talk about JHK hiding in Herpes viruses?

Questions, Questions, Questions, as always!

 

[ukxmrv]

How do they find HIV+ patients who are not on ARV tx?

 

[Bob]

How do they find HIV+ patients who are not on ARV tx?

If they are studying populations in southern Africa, then maybe ARVs are not available, or affordable, to all?