Project 463158

Antiretroviral therapy (ART) blocks HIV replication and extends the life of people living with HIV (PLHIV). However, it does not eliminate the virus from the body, requiring ART lifelong. Therefore, there is a desperate need to develop a cure for HIV infection. HIV achieves long-term persistence by infecting various immune cells that make up the HIV reservoir. Intense studies have focused on the identify and maintenance of the HIV reservoir, but testing of interventions that either eliminate or reduce the size of the HIV reservoir in clinical trials have been met with limited success. These studies highlight the need for an effective and scalable cure strategy for PLHIV. Memory T cells are naturally long-lived and contributes to lifelong immunity against pathogen reinfections. However, HIV targets these cells for infection and appears to take advantage of their natural ability to persistent in the body. In this project, we will investigate how HIV hijacks normal memory T cells, and whether these mechanisms contribute to their long-term persistence in the body. We have developed a new approach that allows us to watch infected T cells in the body. Our goal is to identify the immunological features that contribute to the formation and maintenance of the HIV reservoir in T cells. Together, the proposed studies will reveal important insights into how the HIV reservoir in PLHIV is preserved for many years, and lead to new therapies that can help reverse this process.