Perivascular Macrophages Are the Primary Cell Type Productively Infected by Simian Immunodeficiency Virus in the Brains of Macaques: Implications for the Neuropathogenesis of AIDS

doi:10.1084/jem.193.8.905

Published online 9 April 2001.

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© The Rockefeller University Press, 0022-1007/2001/4/905/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 8, April 16, 2001 905-916

Original Article

Perivascular Macrophages Are the Primary Cell Type Productively Infected by Simian Immunodeficiency Virus in the Brains of Macaques: Implications for the Neuropathogenesis of AIDS

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

Correspondence to: Kenneth C. Williams, Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, RE-113, P.O. Box 15732, Boston, MA 02215. Tel:617-667-2064 Fax:617-667-8210 E-mail:kenneth_williams{at}hms.harvard.edu.

The macrophage is well established as a target of HIV and simianimmunodeficiency virus (SIV) infection and a major contributorto the neuropathogenesis of AIDS. However, the identificationof distinct subpopulations of monocyte/macrophages that carryvirus to the brain and that sustain infection within the centralnervous system (CNS) has not been examined. We demonstrate thatthe perivascular macrophage and not the parenchymal microgliais the primary cell productively infected by SIV. We furtherdemonstrate that although productive viral infection of theCNS occurs early, thereafter it is not easily detectable untilterminal AIDS. The biology of perivascular macrophages, includingtheir rate of turnover and replacement by peripheral blood monocytes,may explain the timing of neuroinvasion, disappearance, andreappearance of virus in the CNS, and questions the abilityof the brain to function as a reservoir for productive infectionby HIV/SIV.

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

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