Unique impact of SIV on monocyte CNS trafficking

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DESCRIPTION (provided by applicant): Monocytes play a central role in the pathogenesis of human immunodeficiency virus (HlV)-associated dementia. They are thought to facilitate viral neuroinvasion, serving as "Trojan horse" for virus entry into the brain. However, many aspects regarding monocyte brain recruitment in HIV infection remain undefined. We hypothesize that a unique monocyte brain migratory program is triggered upon HIV infection (versus infection with other pathogens). Specific aim 1 will define in vitro monocyte migratory profiles triggered upon simian immunodeficiency virus (SIV) infection (compared to infection with CMV, Salmonella and Listeria) in response to CNS-specific chemokine signals which correlate with observed increased fluorescein+ monocyte brain infiltration in vivo. In specific aim 2, I will examine chemokine responses of SIV-infected monocytes to identify autocrine regulatory mechanisms involved in promoting continued monocyte CMS recruitment. My findings are expected to provide novel insights into mechanism(s) of monocyte neuroinvasion in the nonhuman primate model for AIDS and may lead to novel drug targeting or treatment strategies that inhibit aberrant monocyte neuroinfiltration (by targeting specific monocyte subsets or their trafficking signals).