Perivascular macrophages are the primary cell type productively infected by simian immunodeficiency virus in the brains of macaques: Implications forthe neuropathogenesis of AIDS

The macrophage is well established as a target of HIV and simian immunodefi ciency virus (SIV) infection and a major contributor to the neuropathogenes is of AIDS. However, the identification of distinct subpopulations of monoc yte/macrophages that carry virus to the brain and that sustain infection wi thin the central nervous system (CNS) has not been examined. We demonstrate that the perivascular macrophage and not the parenchymal microglia is the primary cell productively infected by SIV. We further demonstrate that alth ough productive viral infection of the CNS occurs early, thereafter it is n ot easily detectable until terminal AIDS. The biology of perivascular macro phages, including their rate of turnover and replacement by peripheral bloo d monocytes, may explain the timing of neuroinvasion, disappearance, and re -appearance of virus in the CNS, and questions the ability of the brain to function as a reservoir for productive infection by HIV/SIV.