Grant: Operating Grant - PA: HIV/AIDS Research Initiative - Biomedical/Clinical Stream

During the course of infection with HIV a population of T helper cells, critical for immune response, are produced which have the viral genome inserted into the cell chromosome, but where the virus is completely shut off. These are known as latently infected cells, sometimes referred to as latency, and this latent virus cannot be eliminated from the body because the immune system doesn't know that it is there. These latently infected cells contribute to disease because replication of the virus becomes turned back on when these cells try and help mount a response to an infection. The continual development of latency and reactivation of the virus ultimately reduces this critical T helper cell population to a level where individuals can no longer fight off common infections. We have identified a factor, called RBF-2 that is critical for controlling the ability of the virus to shut itself off to produce latency, but is also required for turning the virus back on in T helper cells that try to help fight infection. Our results indicate that it does this by organizing the virus DNA, inserted into the chromosome, into specific conformations that allow it to shut itself off and then turn back on again. Our goals are to identify interactions with other proteins that confer these properties, and to evaluate whether drugs that inhibit RBF-2 function might be useful for treating HIV infections. We suggest that RBF-2 inhibitors will be useful in the early stages of infection to prevent the appearance of these latently infected T helper cell populations, or in combination with other drugs to force latent virus out of hiding so that they can be eliminated.