Reactivation of Latent HIV Cells May Lead to Improved Therapeutic Treatments

Researchers at the Gladstone Institute of Virology and Immunology (GIVI) have come up with a way to reactivate latent HIV cells that may lead to the eradication of these cells.

Steven E. Kauder, lead author of the study, and colleagues “developed in vitro models of HIV—1 latency in T cells that harbor a full-length HIV genome.” In addition, the provirus in the cell lines “encoded a fluorescent marker to illuminate HIV-1 transcriptional activity.” Through this process, the researchers discovered that methylation of cytosine in the DNA of the infected cells is tied to HIV latency and reactivation of the virus. Inhibition of DNA methylation with the drug 5-aza-2'deoxycytidine (aza-CdR) was found to reactivate the virus. The researchers also reported that a host protein, methlyl-CpG binding domain protein 2, binds to the methylated HIV DNA and was an “important mediator of latency.”

“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 Kauder.

In an abstract of the article, which appeared in PLoS Pathogens, the researchers reported that this finding is important because current HIV drug therapies reduce the presence of the virus “to an undetectable level.” However, they continued, when drug therapy is stopped, the disease quickly returns, which is due, in part, to latent cells infected with HIV. The ability to reactivate latent HIV cells would allow physicians to reduce or eliminate these “reservoirs” of HIV, which, the researchers said in the journal article, is “necessary.”

“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 Dr. Eric Verdin, GIVI associate director and senior author of the study.

Researchers Alberto Bosque and Vicente Planelles of the University of Utah and Annica Lindqvist of Karolinska University in Sweden also participated in the study.