Researchers discover new approach to flushing out HIV reservoirs

Researchers at the National Cancer Institute, part of the National Institutes of Health, have discovered new information about how HIV evades eradication from the body and have identified possible gene targets and two new drugs that may be effective in flushing out HIV viral reservoirs that other anti-HIV drugs don't affect. "The persistence of latent HIV reservoirs is one of the main barriers to the eradication of HIV infection," principal investigator Steven Zeichner said in a press release. "Our studies show that agents targeting specific genes can be used to force HIV out of latency. In a clinical setting, forcing HIV out of latency while maintaining good control of HIV replication using antiretroviral drugs may reduce or eliminate these reservoirs." In a study published in the August 15 edition of the Journal of Virology, the researchers report that several previously unidentified human genes play a role in HIV replication and that these genes are expressed at very low levels in latently infected human cells, which allows HIV to essentially lurk undetected in the cells and escape the effects of anti-HIV drugs. By "turning on" these genes, the virus in the cells begins replicating, but it also becomes visible to antiretroviral drugs that can disable it. Zeichner and research fellow Vyjayanthi Krishnan used a compound called resveratrol to activate the cellular gene Egr1, which stimulated HIV replication. Their success in stimulating replication in latently infected cells "suggests that there may be additional new ways to manipulate HIV latency and perhaps deplete latently infected reservoirs or even perhaps eliminate HIV infection," Zeichner said. Zeichner's team also examined differences in gene expression between latently infected cells and actively infected cells, generating further possible therapeutic targets. A total of 1,740 genes out of 9,127 studied showed statistically significant differences in expression between latently infected cells and those in which HIV was actively replicating. Some of the genes that were expressed differently in infected cells are genes that have been linked to some cancers, suggesting that HIV requires some of the same functions that are implicated in the development of cancer. Many of these genes are already the subject of drug development efforts directed at cancer and other disorders. While Krishnan cautions that their data are far from clinical application, she believes "the results may provide an early hint at strategies for drugs that target cellular activity rather than the virus itself." Unlike current anti-HIV drugs, such therapies "may be less likely to engender drug resistance by HIV."