The resting, or unreplicating, immune cells that are a major component of the HIV reservoir can clone themselves and give rise to new latently infected cells capable of producing virus. This finding about the reservoir’s ability to proliferate reveals yet another factor that makes curing the virus so extremely difficult.

Latently infected cells remain under the radar of standard antiretroviral (ARV) treatment for HIV because such drugs work only in actively replicating infected cells.

Publishing their findings in The Journal of Experimental Medicine, researchers drew CD4 cells latently infected with HIV from 12 people on long-term ARV treatment. They then grew the cells in the laboratory and exposed them to four rounds of chemicals to stimulate cell division and proliferation.

After each round of stimulation, the scientists divided the cell population into two separate groups, one of which received another round of they chemicals while the other served as a control. After each treatment, they measured whether the cells were actively producing virus.

Received wisdom held that latently infected cells could not proliferate without releasing active HIV. But in this study, the researchers found that each round of stimulation caused some of the cells to produce virus, which suggested that some of the latently infected cells divided without releasing any virus and retained this ability in the face of subsequent stimulations.

Genetic sequencing of the viruses revealed that 57 percent of the viruses had genetic footprints identical to other virus isolates from the same study participant. This strongly suggests that the latently infected cells were proliferating and in the process copying the HIV encoded into their genomes.

“We knew before that the reservoir is very long-lived,” Robert Siliciano, MD, PhD, a professor of medicine at Johns Hopkins University School of Medicine and the study’s lead author, said in a press release, “but what we didn’t know was how the reservoir was maintained. Now it is clear that these cells aren’t just sitting there but are dividing and replenishing themselves.”

In future research, Siliciano and his team intend to investigate the particular factors that lead latently infected cells to proliferate. They also hope to develop new means of studying whether where it is HIV has been integrated into the cellular genome affects this process.

To read a press release about the study, click here.

To read the study, click here.