New Advances in HIV

xmac1x

Ok so I'm doing a biology course in DCU and we were talking about viruses recently. Now I'm under the impression that HIv virus infects the CD4 helper cells. We were also told that if a virus has no host cell to live in then it will inevitably die. So my question is that in a controlled clean environment could a person, infected with HIV, be subjected to a treatment that kills all CD4 cells leaving the virus with no place to live?

Kevster

I've done Microbiology for 4 years now and I believe that - yes - this could work. However, HIV can reside in the lymph nodes too. So, you'd have to remove them also, but this would really mess up the entire immune system of the host. Plus, how would you then stimulate the host to begin producing CD4 cells again if you've removed their lymph nodes?

I'm sure that we would have heard about this kind of therapy if it could work. It's a nice idea though... ...jealous that I didn't think of it!

Kevin

2Scoops

HIV can find many reservoirs within the human body, not just CD4 T cells. It's not even limited to immune cells per se. It would take an incredible effort to eliminate every instance of the virus from an infected individual... and then reconstitute the immune system as well. Theoretically possible, maybe, but virtually impossible in practice.

That said, there was a high profile case recently where a HIV positive patient received a transfusion of haematopoietic bone marrow-derived cells with a mutant CCR5 receptor, making them highly resistant to HIV infection. Around a year later, his viral load tests are coming back negative. Has he really been cured? It's almost certain that there are still copies of the HIV virus in his system. And HIV has several negative effects outside of its influence on the immune system. Time will tell...

http://content.nejm.org/cgi/content/full/360/7/692

Fionnanc

The HIV virus infects, hijacks and destroys the CD4 helper t-cells. The illness/immunodeficieny that HIV produces results in the loss of CD4 cells. In full blown AIDS CD4 counts are near zero, so if you destroy the CD4 cells, the patient has AIDS from the treatment instead of from the HIV.-No benefit.

Modern antiviral drug cocktails kill a lot of virus allowing most of the CD4 T-cells to recover. Sure it will never eliminate the virus but a near normal immune system results with most of the problems coming from drug side-effects rather than the infection

The helper T-cells play an important role in recruiting / modulating the immune response to antigen.

A similar treatment would be a bone marrow transplant for haematological malignancy cure-high mortality and morbidity rate-the anti-HIV drug cocktails would be considered safer and more efficacious.

Tree

It also likes to hang out in macrophages.

Kevster

2Scoops wrote: »

That said, there was a high profile case recently where a HIV positive patient received a transfusion of haematopoietic bone marrow-derived cells with a mutant CCR5 receptor, making them highly resistant to HIV infection. Around a year later, his viral load tests are coming back negative. Has he really been cured? It's almost certain that there are still copies of the HIV virus in his system. And HIV has several negative effects outside of its influence on the immune system. Time will tell...

http://content.nejm.org/cgi/content/full/360/7/692

I heard about that case alright. I suppose that HIV could theoretically insert it's genetic material into any type of cell that it encounters, whether it be one of the immune system or not. Any thoughts?

Prime Mover

The cells would have to express molecules that bind the HIV gp120 glycoprotein in the way that CD4 and CCR5/CXCR4 do.

xmac1x

wow thats a lot of responses, yes I've heard that the virus can reside in the lymph nodes too. Interestingly enough "despite intense HIV-1 exposure, a minority of Nairobi prostitutes remain HIV uninfected, as determined by serology and PCR, and have been defined as HIV resistant"

http://gateway.nlm.nih.gov/MeetingAbstracts/ma?f=102243367.html

SomeDose

2Scoops wrote: »

HIV can find many reservoirs within the human body, not just CD4 T cells. It's not even limited to immune cells per se. It would take an incredible effort to eliminate every instance of the virus from an infected individual... and then reconstitute the immune system as well. Theoretically possible, maybe, but virtually impossible in practice.

That said, there was a high profile case recently where a HIV positive patient received a transfusion of haematopoietic bone marrow-derived cells with a mutant CCR5 receptor, making them highly resistant to HIV infection. Around a year later, his viral load tests are coming back negative. Has he really been cured? It's almost certain that there are still copies of the HIV virus in his system. And HIV has several negative effects outside of its influence on the immune system. Time will tell...

http://content.nejm.org/cgi/content/full/360/7/692

Likewise, certain strains of HIV-1 can bind to cells only via the CCR5 receptor (CCR5-tropic HIV-1), whereas other types can bind via CCR5 and/or CXCR4. This has led to the development of new anti-rets such as Maraviroc which specifically block CCR5. However, at present this necessitates a trofile asssay of the individual's blood prior to starting therapy, which must be sent to the US and takes weeks for a result. The increased prevalence of viral resistance has resulted in plenty of interest in similar novel targets.

Kevster

xmac1x wrote: »

wow thats a lot of responses, yes I've heard that the virus can reside in the lymph nodes too. Interestingly enough "despite intense HIV-1 exposure, a minority of Nairobi prostitutes remain HIV uninfected, as determined by serology and PCR, and have been defined as HIV resistant"

http://gateway.nlm.nih.gov/MeetingAbstracts/ma?f=102243367.html

Yeh, that's amazing isn't it? It's yet more evidence of natural selection/evolution working right now as we speak. I believe that humans have the mindset that we are, like, the end of the line in terms of evolution. However, life is always evolving, selecting the 'fittest' forms given the surrounding conditions.

Kevin

AtomicHorror

Think I read that HIV will infect microglial cells in the CNS also, so that'd be another reservoir.

SomeDose wrote: »

Likewise, certain strains of HIV-1 can bind to cells only via the CCR5 receptor (CCR5-tropic HIV-1), whereas other types can bind via CCR5 and/or CXCR4.

Fuzzy on this as it's been a while but I think it needs CD4 in either case, CCR5 and CXCR4 are co-receptors for the virus and needed for viral entry. A HIV infection contains both strains (and dual tropic too if I remember right) but at differing frequencies during the course of an infection. Initially I think most infections (at least sexually transmitted ones) begin with a CCR5-tropic strain infecting macrophages and DCs, with the declining population of those cells driving selection for CXCR4 co-receptor tropic strains. There's a shift in the virus particle population towards T-tropic HIV (more evolution for Kevster). That brings about increased infection of helper T cells and all the nastiness that comes with the resulting collapse of the adaptive system.

Blocking CCR5 and CXCR4 seems to be the favoured treatment under research these days, perhaps because chemokine receptors share ligands and function to a certain degree, so you always have a backup of sorts. Not sure why CD4 is considered off limits though I'd suspect it may be because its function as a co-receptor during antigen presentation is non-redundant.

SomeDose

AtomicHorror wrote: »

Fuzzy on this as it's been a while but I think it needs CD4 in either case, CCR5 and CXCR4 are co-receptors for the virus and needed for viral entry. A HIV infection contains both strains (and dual tropic too if I remember right) but at differing frequencies during the course of an infection. Initially I think most infections (at least sexually transmitted ones) begin with a CCR5-tropic strain infecting macrophages and DCs, with the declining population of those cells driving selection for CXCR4 co-receptor tropic strains. There's a shift in the virus particle population towards T-tropic HIV (more evolution for Kevster).

Correct, hence why the tropism test is necessary to ensure only CCR5-tropic HIV-1 is detectable prior to treatment with Maraviroc, and periodically thereafter to pick up any resistance and conversion to mixed/dual-tropic strains. The drug is useless against any viral strains that can use CXCR4 as a co-receptor.

DrIndy

This thread will not be hijacked twice.

Please continue folks where we left off.