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* Department of Microbiology, and Medical School, and
Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN 55455;
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104; and
Emory Vaccine Center and Yerkes National Primate Research Center, Atlanta, GA 30322
Primate lentiviruses are typically apathogenic in their evolutionarily coadapted host species but can be lethal when transferred to new host species. Why such infections are pathogenic in humans and rhesus macaques (RMs) but not in sooty mangabeys (SMs), a natural host, remains unclear. Studies of chronically infected animals point to the importance of diminished immune activation in response to the infection in SMs. In this study, we sought the causes and timing of the differences in immune activation in a comparative study of acute SIV infection in RMs and SMs. Surprisingly, we show that in acute infection immune activation is comparable in SMs and RMs but thereafter, SMs quickly resolve immune activation, whereas RMs did not. Early resolution of immune activation in SMs correlated with increased expression of PD-1 and with preservation of CD4+ T cell counts and lymphatic tissue architecture. These findings point to early control of immune activation by host immunoregulatory mechanisms as a major determinant of the different disease outcomes in SIV infection of natural vs non-natural hosts.
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 Grants R01 AI48484 and AI056997 (to A.T.H.), Grants R01 AI66998 and AI52755 (to G.S.), Grant R01 HL75766 (to S.S.), Grant T32 AI07421 (to J.D.E.) from the National Institutes of Health, and by Grant RR0165 from the Yerkes National Primate Research Center. This project has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health under contract N01-CO-12400.
2 The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government.
3 Current address: AIDS Vaccine Program, Science Applications International Corporation–Frederick, National Cancer Institute, Frederick, MD 21702.
4 Address correspondence and reprint requests to Dr. Ashley T. Haase, Department of Microbiology, Mayo Mail Code 196, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN 55455; E-mail address: haase001{at}umn.edu or Dr. Guido Silvestri, 705 Stellar-Chance Laboratories, University of Pennsylvania, 422 Curie Boulevard, Philadelphia, PA 19104; E-mail address: gsilvest{at}mail.med.upenn.edu
5 Abbreviations used in this paper: RM, rhesus macaque; SM, sooty mangabey; TZ, T cell zone; QIA, quantitative image analysis; LT, lymphatic tissue; PD-1, programmed cell death-1.
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  M. Meythaler, A. Martinot, Z. Wang, S. Pryputniewicz, M. Kasheta, B. Ling, P. A. Marx, S. O'Neil, and A. Kaur Differential CD4+ T-Lymphocyte Apoptosis and Bystander T-Cell Activation in Rhesus Macaques and Sooty Mangabeys during Acute Simian Immunodeficiency Virus Infection J. Virol., January 15, 2009; 83(2): 572 - 583. [Abstract] [Full Text] [PDF]
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