A pair of new studies suggest that HIV evolved to enter into a latent state in order to thrive in the long run, and that the virus itself, and not infected immune cells, controls when replication stops and starts, Medical Xpress reports. These findings contrast with prevailing beliefs that HIV’s entry into a non-replicating state, which is a major roadblock to developing a cure for the virus, is ultimately an evolutionary accident and that it is not essential to the virus’s overall survival. Publishing two separate papers in the journal Cell, researchers examined various aspects of viral latency and used computer modeling to come up with their projections about how natural selection favored the rise of the phenomenon.

In one paper, the researchers first showed that the overall viral population remains in an actively replicating state while some cells go dormant. This suggests that the two processes operate independently from one another. Using computer modeling, the researchers identified the HIV-generated protein known as Tat as instrumental to whether the virus went in or out of latency. When the scientists changed the Tat levels in the computer models, they found that it affected whether a cell replicated or not. Changing the state of the infected cell had little or no effect on replication.

In order to verify the findings of this modeling, the scientists manufactured simplified circuits of HIV through synthetic biology and then toyed with the Tat levels. This showed that Tat indeed served as an off or on switch of sorts. Trying directly to relax or activate the infected cell did not have such an effect.

In another paper, researchers pondered the fact that HIV is at high risk of dying out when it comes into initial contact with mucosal tissue—for example, in the rectum—and before it can wind its way into the body and establish a chronic infection. If the virus were to infect and destroy all of the relatively small number of immune cells at this site, it would thwart its own long-term survival, because there would be no more cells in the vicinity to infect; additionally, those cells that were infected would likely die before they could progress further into the body. But should the virus enter a latent state in some cells during this initial phase of infection, it could then survive long enough to generate more virus in an area of the body where there are greater numbers of immune cells, thus generating an indefinite infection and possibly leading to transmission into other people. The researchers were examining a new theory that natural selection has favored HIV that enters a resting state because of this survival advantage.

The researchers used mathematical modeling based upon a financial theory known as “bet-hedging” to weigh the up- and downsides of the virus entering a latent state. Drawing upon data from HIV-positive individuals, the researchers projected that latency benefits the virus and ultimately leads to greater spread through the human population.

To read the Medical Xpress story, click here.