David Margolis, M.D., HDAC inhibition and chromatin remodeling to disrupt proviral latency

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Uploaded by on Dec 1, 2009

Dr. Margolis is working with a group of compounds that may be able to flush HIV out of the body, a goal that constitutes of cornerstone of HIV research. With amfAR's support, he has narrowed down the compounds to a group that looks promising for follow-up, taking us one step closer to eventually finding a cure for HIV. Dr. Rowena Johnston, amfAR's vice president for research, described this innovative work.

For more information please visit www.adopt-a-scientist.com

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  • @ethanhines Inhibiting HDAC would lead to HIV expression which allows antiretroviral therapy to kill the virus. Current antiretroviral therapy cannot kill latent virus. Scientists are searching for markers of latently infected cells, but no marker has been identified that differentiates them sufficiently from any other infection-susceptible cell i.e. there is currently no way to kill only latently or even actively infected cells.

    Rowena Johnston, Ph.D

  • Inhibiting HDAC would lead to HIV expression which allows antiretroviral therapy to kill the virus. Current antiretroviral therapy cannot kill latent virus. Scientists are searching for markers of latently infected cells, but no marker has been identified that differentiates them sufficiently from any other infection-susceptible cell i.e. there is currently no way to kill only latently or even actively infected cells.

  • @AIDSResearch :If HIV permanently integrates it's own genetic code into a CD4+ Tcell, how does inhibiting HDAC which controls access to DNA for host cell protein transcription provide a means to eradicate the infection? Would it not make more sense to develop a drug that marks latent infected cells for destruction via NK cells or induce cellular suicide (apoptosis)?

  • HDAC is histone deacetylase. It takes acetyl away from histone. Histone is a component of genes that gives them their physical structure. If you take acetyl away from histone, it makes the histone, and therefore the genes, bunch up very tightly. The genes, which may be HIV genes, are wound so tightly that they cannot perform their normal function, which is to make proteins. Therefore the HIV is therefore latent, which is another way of saying it is not making proteins.

    Rowena Johnston, Ph.D

  • How does HIV use HDAC to provide latency?

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