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Simian Immunodeficiency Virus SIVagm Dynamics in African Green Monkeys

Divisions of Comparative Pathology,¹ Microbiology,⁴ Veterinary Medicine, Tulane National Primate Research Center, Covington, Louisiana 70433,⁵ Department of Pathology, School of Medicine, Tulane University, New Orleans, Louisiana 70112,² Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico 87545,³ Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19107,⁶ Gilead Sciences, Inc., Foster City, California 94404,⁷ Department of Tropical Medicine, School of Public Health, Tulane University, New Orleans, Louisiana 70112⁸

Received 7 November 2007/ Accepted 15 January 2008

The mechanisms underlying the lack of disease progression in natural simian immunodeficiency virus (SIV) hosts are still poorly understood. To test the hypothesis that SIV-infected African green monkeys (AGMs) avoid AIDS due to virus replication occurring in long-lived infected cells, we infected six animals with SIVagm and treated them with potent antiretroviral therapy [ART; 9-R-(2-phosphonomethoxypropyl) adenine (tenofovir) and beta-2,3-dideoxy-3-thia-5-fluorocytidine (emtricitabine)]. All AGMs showed a rapid decay of plasma viremia that became undetectable 36 h after ART initiation. A significant decrease of viral load was observed in peripheral blood mononuclear cells and intestine. Mathematical modeling of viremia decay post-ART indicates a half-life of productively infected cells ranging from 4 to 9.5 h, i.e., faster than previously reported for human immunodeficiency virus and SIV. ART induced a slight but significant increase in peripheral CD4⁺ T-cell counts but no significant changes in CD4⁺ T-cell levels in lymph nodes and intestine. Similarly, ART did not significantly change the levels of cell proliferation, activation, and apoptosis, already low in AGMs chronically infected with SIVagm. Collectively, these results indicate that, in SIVagm-infected AGMs, the bulk of virus replication is sustained by short-lived cells; therefore, differences in disease outcome between SIVmac infection of macaques and SIVagm infection of AGMs are unlikely due to intrinsic differences in the in vivo cytopathicities between the two viruses.

Published ahead of print on 23 January 2008.

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