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Journal of Virology, April 2005, p. 4043-4054, Vol. 79, No. 7
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.7.4043-4054.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Divergent Host Responses during Primary Simian Immunodeficiency Virus SIVsm Infection of Natural Sooty Mangabey and Nonnatural Rhesus Macaque Hosts

Guido Silvestri,^1,2 Andrew Fedanov,² Stephanie Germon,² Natalia Kozyr,² William J. Kaiser,² David A. Garber,^1,2 Harold McClure,^3, Mark B. Feinberg,^1,2,4 and Silvija I. Staprans^1,2,4*

Departments of Medicine,¹ Microbiology and Immunology,⁴ Emory Vaccine Center, Emory University School of Medicine,² Yerkes National Primate Research Center of Emory University, Atlanta, Georgia³

Received 5 October 2004/ Accepted 11 November 2004

To understand how natural sooty mangabey hosts avoid AIDS despite high levels of simian immunodeficiency virus (SIV) SIVsm replication, we inoculated mangabeys and nonnatural rhesus macaque hosts with an identical inoculum of uncloned SIVsm. The unpassaged virus established infection with high-level viral replication in both macaques and mangabeys. A species-specific, divergent immune response to SIV was evident from the first days of infection and maintained in the chronic phase, with macaques showing immediate and persistent T-cell proliferation, whereas mangabeys displayed little T-cell proliferation, suggesting subdued cellular immune responses to SIV. Importantly, only macaques developed CD4⁺-T-cell depletion and AIDS, thus indicating that in mangabeys limited immune activation is a key mechanism to avoid immunodeficiency despite high levels of SIVsm replication. These studies demonstrate that it is the host response to infection, rather than properties inherent to the virus itself, that causes immunodeficiency in SIV-infected nonhuman primates.

Deceased.

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