IN VIVO DEPLETION OF CD16+ MONOCYTES IN SIV INFECTED MACAQUES

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Undetectable levels of virus in the plasma of HIV infected patients can be achieved on seemingly effective antiretroviral therapy. However, patients that have terminated treatment, either because of intolerance or noncompliance, experience a rapid resurgence of viral burden, underscoring the role of reservoirs where the virus hide and persists. One such cellular reservoir is monocyte/macrophage lineage cells. Infected monocytes traffic to tissues and become macrophages, which are a major cell type infected in non-lymphoid organs such as the brain, heart and kidney. A subset of blood monocytes expressing the CD16 antigen expands in HIV infected humans and SIV infected macaques, and preferentially harbor virus. It has been hypothesized that the infection and traffic of CD16+ monocytes play a key role in the pathogenesis of neurologic dysfunction associated with HIV infection. For a direct demonstration of their pathogenic role, however, depletion of these cells will be required. Therefore, we propose to use a SIV/macaque model of neuroAIDS (rhesus monkeys that are SIV infected, CD8 lymphocyte depleted) with an antibody that kills CD16+ monocytes and therefore would block their traffic to tissues. Previously using this animal model, we found that biphasic expansion of CD16+ monocytes during primary infection and during progression to AIDS correlates with brain neuronal injury. The main objective of this project is to determine the effects of CD16+ monocyte depletion on HIV induced brain disease and virus infection in macrophages. Anti-CD16 antibody treatment, if found effective, could be used in combination with the existing antiretroviral regimen to eliminate residual viral reservoirs in HIV infected patients.