Grant: Doctoral Research Award - PA: Biomedical/Clinical HIV/AIDS Research

HIV infection is marked by low or lack of immunity which allows infections to enter and persist in the body. The link between HIV infection and lack of immunity is clear. However, it is not fully understood at the molecular level. HIV disrupts many processes and mechanisms in the white blood cells. One of the mechanisms that is impaired by HIV and is crucial for body immunity is mediated by Interleukin (IL)-7. IL-7 is a 'messenger' molecule which is produced when an infection enters the body and travels through the blood stream to alert immune cells to the presence of the invader. Some immune cells, including CD8 T-cells, have a special receptor on their surface that allows them to detect IL-7 and respond to the alarm. We recently showed that one of the HIV products, the Tat protein, is able to bind to the IL-7 receptor and remove it from the surface of CD8 T-cells. As a result, the CD8 T-cells cannot "hear" the alarm and fail to activate in the presence of infection leaving the body vulnerable. In this study, we will first identify the details of how IL-7 helps CD8 T-cells to grow and become functional. Then we will examine the effects of IL-7 in presence of the HIV Tat protein. The main goal of this project is to identify the exact effects of Tat on CD8 T-cell functions. If we understand how IL-7 activates CD8 T-cells and how HIV disables them, we may be able to design drugs that could reverse the effect and restore immune function in HIV+ patients.