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

HIV infection resulting in Acquired Immunodeficiency Syndrome (AIDS) is dramatically affecting the health of nations worldwide. People infected with HIV progressively lose the function of their immune system and the ability to recover from disease. The virus incapacitates the patients' immune system in a variety of ways, one of which is its ability to enter immune cells mainly T cells, monocytes and macrophages. The virus can remain inside these cells, effectively hiding from current anti-HIV treatment therapies, as well as the patients' immune system. Therefore one of the many challenges facing scientists is how to eliminate virus from these cells. HIV infection normally kills immune T cells; however, monocytes/macrophages are somehow able to survive HIV infection. One of the HIV proteins, termed Vpr, has been shown to cause cell death in T cells and neuronal cells. Our preliminary results show that this protein can also kill monocytes but not differentiated macrophages. It is well known that HIV patients get infected with opportunistic infections primarily because of their deficient immune system. These patients contain various microbial products including bacterial DNA in their blood. We have found that when patient's monocytes come in contact with microbial products such as their DNA (CpG) cannot be killed by Vpr protein. Overall, this proposal is directed towards understanding mechanisms by which monocytes/macrophages are essentially protected from death caused by the killing effect of either HIV or its viral proteins. The results of this study will help in understanding how macrophages evade the killing effect of HIV or its toxic proteins such as Vpr with a view to designing novel strategies that may prove useful towards HIV eradication from infected people.