A key mechanism that regulates HIV latency has been discovered by Gladstone researchers. This discovery may lead to eradication of HIV from infected patients who have been on antiretroviral therapy.
The real cure for HIV has been elusive because the virus can "hide" in a latent form in resting CD4-T cells.
AdvertisementBy understanding this "latency" effect, researchers can identify ways to reactivate the virus and enable complete clearance by current or future therapies.
The study showed that methylation of cytosine in the DNA of infected cells is associated with HIV latency and inhibition of DNA methylation causes the reactivation of latent HIV.
"While HIV-1 latency is likely to be a multifactorial process, we have shown that inhibiting the methylation of the provirus contributes to an almost complete reactivation of latent HIV-1," said lead author Steven E. Kauder.
In addition to finding that DNA methylation is a mechanism of latency, the scientists also discovered that a host protein, called methlyl-CpG binding domain protein 2 (MBD2) binds to the methylated HIV DNA and is an important mediator of latency.
"Interfering with methylation greatly potentiates the reactivation of HIV," said Kauder.
In this study, the researchers found that the drug 5-aza-2'deoxycytidine (aza-CdR) can inhibit HIV methylation and cause the virus to reactivate.
"Combined with other areas of our investigation into HIV latency, this research provides important new knowledge about the process and opens many new pathways for future study," said GIVI Associate Director Eric Verdin, MD, senior author of the study.
The discovery was reported in the current edition of PloS Pathogens.