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Original Article

Kenneth C. Williams^a, Sarah Corey^a, Susan V. Westmoreland^a, Doug Pauley^a, Heather Knight^a, Colin deBakker^a, Xavier Alvarez^a, and Andrew A. Lackner^a

^a Division of Comparative Pathology, New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772
Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, RE-113, P.O. Box 15732, Boston, MA 02215.617-667-8210617-667-2064

kenneth_williams{at}hms.harvard.edu

The macrophage is well established as a target of HIV and simian immunodeficiency virus (SIV) infection and a major contributor to the neuropathogenesis of AIDS. However, the identification of distinct subpopulations of monocyte/macrophages that carry virus to the brain and that sustain infection within 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 although productive viral infection of the CNS occurs early, thereafter it is not easily detectable until terminal AIDS. The biology of perivascular macrophages, including their rate of turnover and replacement by peripheral blood monocytes, may explain the timing of neuroinvasion, disappearance, and reappearance of virus in the CNS, and questions the ability of the brain to function as a reservoir for productive infection by HIV/SIV.

Key Words: central nervous system • microglia • brain macrophage • neuropathogenesis • HIV

© 2001 The Rockefeller University Press

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