Difficulties in understanding the mechanisms of HIV neuropathogenesis include the inability to study dynamic processes of infection, cumulative effects of the virus, and contributing host immune responses. We used 1H magnetic resonance spectroscopy and studied monocyte activation and progression of CNS neuronal injury in a CD8 lymphocyte depletion model of neuroAIDS in SIV-infected rhesus macaque monkeys. We found early, consistent neuronal injury coincident with viremia and SIV infection/activation of monocyte subsets and sought to define the role of plasma virus and monocytes in contributing to CNS disease. Antiretroviral therapy with essentially non–CNS-penetrating agents resulted in slightly decreased levels of plasma virus, a significant reduction in the number of activated and infected monocytes, and rapid, near-complete reversal of neuronal injury. Robust macrophage accumulation and productive virus replication were found in brains of infected and CD8 lymphocyte–depleted animals, but no detectable virus and few scattered infiltrating macrophages were observed in CD8 lymphocyte–depleted animals compared with animals not receiving antiretroviruses that were sacrificed at the same time after infection. These results underscore the role of activated monocytes and monocyte infection outside of the brain in driving CNS disease.
Kenneth Williams, Susan Westmoreland, Jane Greco, Eva Ratai, Margaret Lentz, Woong-Ki Kim, Robert A. Fuller, John P. Kim, Patrick Autissier, Prahbat K. Sehgal, Raymond F. Schinazi, Norbert Bischofberger, Michael Piatak Jr., Jeffrey D. Lifson, Eliezer Masliah, R. Gilberto González
Title and authors | Publication | Year |
---|---|---|
NeuroAIDS, Drug Abuse, and Inflammation: Building Collaborative Research Activities
JW Berman, MJ Carson, L Chang, BM Cox, HS Fox, RG Gonzalez, GR Hanson, KF Hauser, WZ Ho, JS Hong, EO Major, WF Maragos, E Masliah, JC McArthur, DB Miller, A Nath, JP OCallaghan, Y Persidsky, C Power, TJ Rogers, W Royal |
Journal of Neuroimmune Pharmacology | 2006 |
Longitudinal analysis of activation markers on monocyte subsets during the development of simian immunodeficiency virus encephalitis
SJ Bissel, G Wang, AM Trichel, M Murphey-Corb, CA Wiley |
Journal of Neuroimmunology | 2006 |
Longitudinal analysis of monocyte/macrophage infection in simian immunodeficiency virus-infected, CD8+ T-cell-depleted macaques that develop lentiviral encephalitis
SJ Bissel, G Wang, AM Trichel, M Murphey-Corb, CA Wiley |
The American Journal of Pathology | 2006 |
Rho-mediated regulation of tight junctions during monocyte migration across the blood-brain barrier in HIV-1 encephalitis (HIVE)
Y Persidsky, D Heilman, J Haorah, M Zelivyanskaya, R Persidsky, GA Weber, H Shimokawa, K Kaibuchi, T Ikezu |
Blood | 2006 |
New Insights into the Neuroimmunity of SIV Infection by Magnetic Resonance Spectroscopy
RG González, JB Greco, J He, MR Lentz, S O'Neil, SJ Pilkenton, EM Ratai, S Westmoreland |
Journal of Neuroimmune Pharmacology | 2006 |
The engagement of activating FcgammaRs inhibits primate lentivirus replication in human macrophages
David A, Sáez-Cirión A, Versmisse P, Malbec O, Iannascoli B, Herschke F, Lucas M, Barré-Sinoussi F, Mouscadet JF, Daëron M, Pancino G |
Journal of immunology (Baltimore, Md. : 1950) | 2006 |