Why can HIV remain latent in the body?
HIV is hard to battle, in part because the virus can lie dormant, or latent, in infected cells for a long period of time. Through this mechanism, HIV evades the toxic effects of therapies and the attacks of the immune system. Disrupting HIV latency is therefore a potential therapeutic strategy.
HIV latency is regulated by an epigenetic mechanism called histone crotonylation that controls gene expression, according to a new study (HIV latency is reversed by ACSS2-driven histone crotonylation) published in the Journal of Clinical Investigation (JCI) on February 19, 2018. This study suggests that histone crotonylation can be targeted for HIV eradication.
Enormous progress has been made in improving HIV treatment and reducing HIV deaths. Antiretroviral therapy (ART) allows many HIV-positive people to live longer and healthier lives. Additionally, this therapy also helps prevent transmission of HIV. Now, HIV infection is largely a chronic disease. But, ART drugs do not kill or cure the virus. There are still a large number of people living with HIV.
Why HIV can remain latent in host cells is a long-standing mystery. If scientists can resolve this mystery, they may be able to find approaches to kick and kill HIV. A cure for HIV/AIDS has long been an important goal of medicine.
Studies have shown that viral latency is epigenetically regulated, but the regulatory effects of epigenetic modifications on transcription and latency of HIV are not fully defined. In the new study, Dr. Satya Dandekar from UC Davis and collaborators demonstrated that the epigenetic mechanism histone crotonylation is involved in the establishment of HIV latency. In addition, they demonstrated that reactivation of latent HIV was achieved after the induction of histone crotonylation through increased expression of ACSS2.
, short for acyl-CoA synthetase short-chain family member 2, is an enzyme that is involved in lipid metabolism and energy generation. Given that HIV infection is often associated with particular unbalances in lipid levels, ACSS2 may be a potential target for treatments of HIV.
Findings of the new study confirm that ACSS2 plays a key role in the regulation of HIV transcription and latency. The researchers concluded that their study "links the HIV/SIV infection–induced fatty acid enzyme ACSS2 to HIV latency and identifies histone lysine crotonylation as a novel epigenetic regulator for HIV transcription that can be targeted for HIV eradication."
Furthermore, combining histone crotonylation with other mechanisms that reactivate HIV may be a more effective approach to disrupt HIV latency. This approach would help scientists find a cure for HIV in the future.
HIV is a serious health problem worldwide. HIV attacks the body's immune system, and over time, it may weaken the immune system. As a result, the patients are susceptible to health problems, such as cancer. When HIV remains latent in host cells, the virus is nearly impossible to target with ART drugs. So, scientists want to disrupt HIV latency in order to make the virus to be attacked by therapies as well as immune responses.