Links between Progressive HIV-1 Infection of Humanized Mice and Viral Neuropathogenesis

Few rodent models of human immunodeficiency virus type one (HIV 1) infection can reflect the course of viral infection in humans To this end we investigated the relationships between progressive HIV 1 infection immune compromise and neuroinflammatory responses In NOD/scid IL-2R gamma(null)(c) mice reconstituted with human hematopoietic CD34(+) stem cells Human blood borne macrophages repopulated the meninges and perivascular spaces of chimeric animals Viral infection in lymphoid tissue led to the accelerated entry of human cells Into the brain marked neuroinflammation and HIV 1 replication in human mononuclear phagocytes A meningitis and less commonly an encephalitis followed cM T807 antibody mediated CD8(+) cell depletion We conclude that HIV 1 infected NOD/scid IL-2R gamma(null)(c) humanized mice can at least in part recapitulate lentiviral neuropathobiology This model of neuroAIDS reflects the virological immunological and early disease associated neuropathological components of human disease (Am J Pathol 2010 177 2938-2949 DOI 10 2353/ajpath 2010.100536)