Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 193, Issue 8, Pages 905-915Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.193.8.905
Keywords
central nervous system; microglia; brain macrophage; neuropathogenesis; HIV
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Funding
- NCRR NIH HHS [K26 RR000168, RR00168, P51 RR000168] Funding Source: Medline
- NINDS NIH HHS [NS30769, NS35732, R01 NS040237, NS40237, R01 NS030769, R01 NS037654, NS37654] Funding Source: Medline
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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 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.
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