Pontential new target for HIV MEDS with A3G
Oct 22, 2008
Hi Dr Keith, thank you for your time and work you put into helping people with hiv, What can you let us know about A3G and maybe changing the way we compat hiv.. thank you once again Anton
Scientists continue to unravel a potential new target for HIV therapy
In pursuit of answers to a rare immune system disease called HIgM-2, scientists at the University of Southern California have developed the first three-dimensional molecular model of a human protein that is able to mutate the genes of retroviruses, including HIV. The study results were first published online by the journal, Nature.
The protein, called APOBEC3G or A3G, is found within all human cells and can interfere with viruses by changing their DNA. It incorporates itself into virus particles and damages their developing genetic material. This new model offers important clues on how and where A3G binds to HIVs DNA. APOBEC3G is part of the larger APOBEC family of protective cell proteins and stands for apoliprotein B mRNA-editing enzyme catalytic polypeptide-like 3G.
Although A3G has been studied since its discovery in 2002, the USC team is the first to create a model of its atomic structure. Surprisingly, it resembles a butterfly. This model can lead scientists to better understand the proteins role in protecting a cell from viral infection. This could eventually lead to treatments for many immune diseases, such as HIV.
In HIV disease, A3G can actually restrict the virus from making more of itself. However, it appears that HIV has developed its Vif (viral infectivity factor) gene to overcome the protective effects of A3G. HIV eventually degrades how well A3G functions within cells in the great majority of people living with HIV, similar to how it mutates in ways to work around the effects of anti-HIV drugs.
Two forms of A3G were uncovered in 2006. The simpler version is found in resting cells or in those CD4 and other immune cells that are not dividing. Although HIV can infect resting cells, most of the time this HIV doesnt produce more virus. This may be due in part to the simpler form of A3G found in these cells having some level of anti-HIV effect.
A more complex form of A3G is found in active cells or in those immune cells that are dividing. HIV can replicate well within these cells. Here, it appears that Vif not only binds to A3G but also signals the immune cell to produce much less of the protein. This enables HIV to reproduce more freely without the natural protection of A3G.
As with most science, promising ideas may not lead to quick victories. Understanding how proteins work is the first step. How to alter a natural body process or deliver a drug that mimics the proteins effect is the next step, but it can be wrought with problems. In this case, how much of which form of A3G is necessary to stop HIV from reproducing? Does using the simpler form of the protein result in activating a greater number of resting cells? What side effects would result?
Although many questions need to be answered, A3G presents a fascinating potential for HIV therapy. It would help unlock a persons innate ability to fight HIV. We were born with it, and its there waiting, stated Xiaojiang Chen, lead author of the study.
Most current HIV drugs target the enzymes that HIV needs in order to reproduce, such as protease and reverse transcriptase. However, a treatment based with A3G would use a human protein rather than an HIV enzyme. Exploiting its potential in this way may lead to a more durable, and perhaps less toxic, treatment for HIV disease
Response from Dr. Henry
This is a promising new target for anti-HIV drug development but there is no A3G-related candidate drug currently under clinical (human) study that would likely be avalable in the near future. Current therapy available in resource weathly areas provides a number of effective options with generally excellent outcomes (viral replication shut down, stabilization/usually reversal of immune damanage/clinical protection against AIDS, good tolerability). KH
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