Cellular Tropism & Reservoir in Brain with HIV-Clade C

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): Studies from populations infected with HIV-clade B virus suggest that patients often develop a dementing illness with important socioeconomic consequences. However, the most common HIV infection worldwide is with HIV-clade C and very little information is available with regards to its neurological manifestations. An important difference between the two clades is that HIV-clade C is nearly exclusively chemokine receptor CCR5 tropic. Since CCR5 expressing cells are present in the central nervous system predominantly in microglia and to a lesser degree in astrocytes, neurons and endothelial cells, it is important to determine the cellular tropism of this virus in brain of HIV-clade C infected patients. Populations infected with HIV-clade C have a high incidence of opportunistic infections and this is often the presenting manifestation of HIV infection. Another important question that remains unanswered is that do HIV infected cells invade the brain during the course of a CNS opportunistic infection? Since the types of cells that make up the inflammatory infiltrates may be different for the various opportunistic infections, it is also important to determine which patients may be at a greater risk for developing HIV encephalitis following treatment of the opportunistic infections. A major obstacle to studying the neuropathological consequences of HIV-clade C infection has been the lack of neurological, neuroradiological or neuropathological services available in areas and populations infected with this virus. The National Institute of Mental Health and Neurosciences in Bangalore, India is unique because all the above services are available at this institute and it has an established brain bank. A unique feature if this brain bank is it has short autopsy times, of 2-8 hours in most cases. Hence, we propose to augment the existing facilities, establish assays for detection and quantification of HIV in brain tissue by immunohistopathology, in situ hybridization, RT-PCR and quantitation of proviral DNA to address the above questions. We believe this will serve as a nidus for the development of several projects to address the neuropathogenesis of HIV infection and develop a rational design for therapeutic approaches and vaccine development.