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* Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104;
Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329;
Division of Experimental Therapeutics, University Health Network, Toronto, Ontario, Canada;
Human Immunology Section, Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892;
¶ University of Texas Southwestern, Dallas, TX 75390;
|| Tulane National Primate Research Center, Tulane Health Sciences Center, Tulane University, Covington, LA 70433; and
# Merck & Co, Vaccine Division, West Point, PA 19486
HIV-infected humans and SIV-infected rhesus macaques experience a rapid and dramatic loss of mucosal CD4+ T cells that is considered to be a key determinant of AIDS pathogenesis. In this study, we show that nonpathogenic SIV infection of sooty mangabeys (SMs), a natural host species for SIV, is also associated with an early, severe, and persistent depletion of memory CD4+ T cells from the intestinal and respiratory mucosa. Importantly, the kinetics of the loss of mucosal CD4+ T cells in SMs is similar to that of SIVmac239-infected rhesus macaques. Although the nonpathogenic SIV infection of SMs induces the same pattern of mucosal target cell depletion observed during pathogenic HIV/SIV infections, the depletion in SMs occurs in the context of limited local and systemic immune activation and can be reverted if virus replication is suppressed by antiretroviral treatment. These results indicate that a profound depletion of mucosal CD4+ T cells is not sufficient per se to induce loss of mucosal immunity and disease progression during a primate lentiviral infection. We propose that, in the disease-resistant SIV-infected SMs, evolutionary adaptation to both preserve immune function with fewer mucosal CD4+ T cells and attenuate the immune activation that follows acute viral infection protect these animals from progressing to AIDS.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health Grants RO1 AI052755 and AI066998 (to G.S.), R01 HL075766 (to S.I.S.), R01 AI035522 and R21 AI060451 (to D.L.S.), R01 AI064066 (to I.V.P.), and RR-00165 (Yerkes National Primate Research Center). S.N.G. was supported by Grant 1F31AI066400-01A1; J.M.M. was supported in part by a training grant from the National Institute of Allergy and Infectious Diseases, 5 T32 AI 07520.
2 Address correspondence and reprint requests to Dr. Guido Silvestri, University of Pennsylvania, 705 Stellar-Chance Laboratories, 422 Curie Boulevard, Philadelphia, PA 19104. E-mail address: gsilvest{at}mail.med.upenn.edu
3 Abbreviations used in this paper: RM, rhesus macaques; BAL, bronchoalveolar lavage; FTC, β-2',3'-dideoxy-3'-thia-5-fluorocytidine; LN, lymph node; MALT, mucosal-associated lymphoid tissues; PB, peripheral blood; PMPA, 9-R-(2-phosphonomethoxypropyl) adenine; RB, rectal biopsy; SM, sooty mangabey.
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