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

[AIDSResearch]

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.

[ethanhines]

How does HIV use HDAC to provide latency?

[AIDSResearch]

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

[ethanhines]

@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)?

[AIDSResearch]

@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