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. The focus of this study is on the perivascular macrophage as target of productive SIV infection in the central nervous system (CNS). Increasing evidence underscores the role of CNS macrophages, some of which are HIV infected, contributing to neurologic disease. We propose that CNS perivascular macrophages are a primary cell productively infected early and terminally, in animals with AIDS and SIV encephalitis (SIVE). We have established previously, using combinations of immune markers expressed by cells of the myeloid lineage, phenotypic differences between perivascular macrophages and parenchymal microglia and identified perivascular macrophages as a primary target of productive SIV infection. The working hypothesis that guides this proposal is that bone marrow monocyte/macrophages that are potential CNS perivascular macrophages, can be identified in SIV infected macaques and studied as they traffic to the CNS. We hypothesize that the immune system controls the level of SIV infection of perivascular macrophage precursors in the bone marrow; their activation traffic through the blood, and accumulation in the CNS. Lastly, we hypothesize that the traffic and accumulation of SIV infected perivascular macrophages, after the development of AIDS, and not SIV that enters the CNS early after infection, correlate with neuronal damage and injury.
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