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Journal of Virology, January 2009, p. 572-583, Vol. 83, No. 2
0022-538X/09/$08.00+0     doi:10.1128/JVI.01715-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Differential CD4⁺ T-Lymphocyte Apoptosis and Bystander T-Cell Activation in Rhesus Macaques and Sooty Mangabeys during Acute Simian Immunodeficiency Virus Infection

Mareike Meythaler,^1,4 Amanda Martinot,² Zichun Wang,¹ Sarah Pryputniewicz,¹ Melissa Kasheta,¹ Binhua Ling,³ Preston A. Marx,³ Shawn O'Neil,² and Amitinder Kaur^1*

Divisions of Immunology,¹ Comparative Pathology, New England Primate Research Center, Harvard Medical School, One Pine Hill Drive, Southborough, Massachusetts 01772,² Division of Microbiology, Tulane National Primate Research Center, Covington, Louisiana 70433,³ Institut für Klinische und Molekulare Virologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Schlossgarten 4, 91054 Erlangen, Germany⁴

Received 12 August 2008/ Accepted 23 October 2008

In contrast to pathogenic lentiviral infections, chronic simian immunodeficiency virus (SIV) infection in its natural host is characterized by a lack of increased immune activation and apoptosis. To determine whether these differences are species specific and predicted by the early host response to SIV in primary infection, we longitudinally examined T-lymphocyte apoptosis, immune activation, and the SIV-specific cellular immune response in experimentally infected rhesus macaques (RM) and sooty mangabeys (SM) with controlled or uncontrolled SIV infection. SIVsmE041, a primary SIVsm isolate, reproduced set-point viremia levels of natural SIV infection in SM but was controlled in RM, while SIVmac239 replicated to high levels in RM. Following SIV infection, increased CD8⁺ T-lymphocyte apoptosis, temporally coinciding with onset of SIV-specific cellular immunity, and elevated plasma Th1 cytokine and gamma interferon-induced chemokine levels were common to both SM and RM. Different from SM, SIV-infected RM showed a significantly higher frequency of peripheral blood activated CD8⁺ T lymphocytes despite comparable magnitude of the SIV-specific gamma interferon enzyme-linked immunospot response. Furthermore, an increase in CD4⁺ and CD4^–CD8^– T-lymphocyte apoptosis and plasma tumor necrosis factor-related apoptosis-inducing ligand were observed only in RM and occurred in both controlled SIVsmE041 and uncontrolled SIVmac239 infection. These data suggest that the "excess" activated T lymphocytes in RM soon after SIV infection are predominantly of non-virus-specific bystander origin. Thus, species-specific differences in the early innate immune response appear to be an important factor contributing to differential immune activation in natural and nonnatural hosts of SIV infection.

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* Corresponding author: Mailing address: Division of Immunology, New England Primate Research Center, Harvard Medical School, One Pine Hill Drive, Southborough, MA 01772. Phone: (508)-624-8169. Fax: (508)-624-8172. E-mail: amitinder_kaur{at}hms.harvard.edu

Published ahead of print on 5 November 2008.

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Journal of Virology, January 2009, p. 572-583, Vol. 83, No. 2
0022-538X/09/$08.00+0     doi:10.1128/JVI.01715-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.