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Journal of Virology, December 1998, p. 9597-9611, Vol. 72, No. 12
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Diverse Host Responses and Outcomes following Simian Immunodeficiency Virus SIVmac239 Infection in Sooty Mangabeys and Rhesus Macaques

Amitinder Kaur,1,2 Robert M. Grant,3,4 Robert E. Means,5 Harold McClure,6 Mark Feinberg,7 and R. Paul Johnson1,2,*

Divisions of Immunology1 and Microbiology,5 New England Regional Primate Research Center, Harvard Medical School, Southborough, and Infectious Disease Unit and AIDS Research Center, Massachusetts General Hospital, Boston,2 Massachusetts; Gladstone Institute of Virology and Immunology3 and Department of Medicine,4 University of California, San Francisco, California; and Divisions of Research Resources and Microbiology and Immunology, Yerkes Regional Primate Research Center,6 and Departments of Medicine and Microbiology & Immunology,7 Emory University, Atlanta, Georgia

Received 15 June 1998/Accepted 24 August 1998

Sooty mangabeys naturally infected with simian immunodeficiency virus (SIV) do not develop immunodeficiency despite the presence of viral loads of 105 to 107 RNA copies/ml. To investigate the basis of apathogenic SIV infection in sooty mangabeys, three sooty mangabeys and three rhesus macaques were inoculated intravenously with SIVmac239 and evaluated longitudinally for 1 year. SIVmac239 infection of sooty mangabeys resulted in 2- to 4-log-lower viral loads than in macaques and did not reproduce the high viral loads observed in natural SIVsmm infection. During acute SIV infection, polyclonal cytotoxic T-lymphocyte (CTL) activity coincident with decline in peak plasma viremia was observed in both macaques and mangabeys; 8 to 20 weeks later, CTL activity declined in the macaques but was sustained and broadly directed in the mangabeys. Neutralizing antibodies to SIVmac239 were detected in the macaques but not the mangabeys. Differences in expression of CD38 on CD8+ T lymphocytes or in the percentage of naive phenotype T cells expressing CD45RA and CD62L-selection did not correlate with development of AIDS in rhesus macaques. In macaques, the proportion of CD4+ T lymphocytes expressing CD25 declined during SIV infection, while in mangabeys, CD25-expressing CD4+ T lymphocytes increased. Longitudinal evaluation of cytokine secretion by flow cytometric analysis of unstimulated lymphocytes revealed elevation of interleukin-2 and gamma interferon in a macaque and only interleukin-10 in a concurrently infected mangabey during acute SIV infection. Differences in host responses following experimental SIVmac239 infection may be associated with the divergent outcome in sooty mangabeys and rhesus macaques.

* Corresponding author. Mailing address: New England Regional Primate Research Center, Harvard Medical School, One Pine Hill Dr., P.O. Box 9102, Southborough, MA 01772. Phone: (508) 624-8148. Fax: (508) 624-8172. E-mail: paul_johnson{at}hms.harvard.edu.

Journal of Virology, December 1998, p. 9597-9611, Vol. 72, No. 12
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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