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JVI Accepts, published online ahead of print on 23 January 2008
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J. Virol. doi:10.1128/JVI.02402-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

SIVagm Dynamics in African Green Monkeys

Ivona Pandrea*, Ruy M. Ribeiro, Rajeev Gautam, Thaidra Gaufin, Melissa Pattison, Mary Barnes, Christopher Monjure, Crystal Stoulig, Jason Dufour, Wayne Cyprian, Guido Silvestri, Michael D. Miller, Alan S. Perelson, and Cristian Apetrei

Divisions of Comparative Pathology, Microbiology, and Veterinary Medicine Tulane National Primate Research Center, Covington Louisiana 70433, USA; Department of Pathology, School of Medicine, Tulane University, New Orleans, Louisiana 70112, USA; Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545, USA; Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19107, USA; Gilead Sciences, Inc, Foster City, California 94404, USA; Department of Tropical Medicine, School of Public Health, Tulane University, New Orleans, Louisiana 70112, USA

* To whom correspondence should be addressed. Email: ipandrea{at}tulane.edu.


   Abstract

The mechanisms underlying the lack of disease progression in natural SIV hosts are still poorly understood. To test the hypothesis that SIV-infected 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: (PMPA, tenofovir) and (FTC, emtricitabine)]. All AGMs showed a rapid decay of plasma viremia that became undetectable 36 hours after ART initiation. Significant decrease of viral load was observed in PBMCs 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 HIV 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 LNs and intestine. Similarly, ART did not significantly change the levels of cell proliferation, activation and apoptosis, already low in chronically SIVagm-infected AGMs. 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 of the in vivo cytopathicity between the two viruses.




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