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

HIV infects a critical type of cells in the immune system, known as T-helper memory cells. These cells remember prior infections, and help fight off new infections of the same type in the future. If left untreated, these cells are gradually killed off by virus replication, and eventually infected people lose the ability to fight off even common infections. The current drugs for HIV can prevent virus replication, and patients are able to live relatively normal lives, but are destined to remain on the drugs for the rest of their life. This is because, during HIV infection some T-helper cells are produced where the HIV genome is inserted into the cell chromosome but virus replication is completely shut off, a property known as latency. The virus in these latently infected cells is unaffected by drug treatment, and can remain hidden in this way for many years. However, when treatment is removed the virus rapidly emerges to replicate again and produce new virus. Consequently, the current drugs do not represent a cure for HIV/AIDS. Additionally, some people do not tolerate the drugs very well, and there are already virus mutants that are resistant to the drugs. Consequently to prevent an uncontrollable resurgence of the HIV epidemic in the future it is necessary to develop new therapies that can eliminate latently infected cells from patients. Our research is designed to identify mechanisms by which the virus can shut itself off once it has inserted into the cell chromosome to produce latency, and how it is able to re-start replication when therapy is removed. We will focus on the function of proteins known as RBF-2 and YY1 that bind to sequences on the viral DNA control region, and which we have previously shown to have important functions for determining whether the virus is shut off or becomes re-activated. We propose that novel drugs that interfere with these proteins could be used as new treatments to eliminate the latently infected cells from patients.