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Journal of Virology, July 2005, p. 8878-8885, Vol. 79, No. 14
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.14.8878-8885.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Pathogenicity of Simian-Human Immunodeficiency Virus SHIV-89.6P and SIVmac Is Attenuated in Cynomolgus Macaques and Associated with Early T-Lymphocyte Responses

Keith A. Reimann,1* Robert A. Parker,2 Michael S. Seaman,1 Kristin Beaudry,1 Margaret Beddall,1 Lauren Peterson,1 Kenneth C. Williams,1 Ronald S. Veazey,3 David C. Montefiori,4 John R. Mascola,5 Gary J. Nabel,5 and Norman L. Letvin1

Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215,1 Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts 02115,2 Tulane National Primate Research Center, Covington, Louisiana 70433,3 Duke University Medical Center, Durham, North Carolina 27710,4 Vaccine Research Center, National Institutes of Health, Bethesda, Maryland 208925

Received 7 February 2005/ Accepted 12 April 2005

Because most studies of AIDS pathogenesis in nonhuman primates have been performed in Indian-origin rhesus macaques (Macaca mulatta), little is known about lentiviral pathogenicity and control of virus replication following infection of alternative macaque species. Here, we report the consequences of simian-human immunodeficiency virus SHIV-89.6P and SIVmac251 infection in cynomolgus (Macaca fascicularis) and rhesus macaques of Chinese origin. Compared to the pathogenicity of the same viruses in Indian rhesus macaques, both cynomolgus and Chinese rhesus macaques showed lower levels of plasma virus. By 9 to 10 months after infection, both viruses became undetectable in plasma more frequently in cynomolgus than in either Chinese or Indian rhesus macaques. Furthermore, after SHIV-89.6P infection, CD4+ T-cell numbers declined less and survival was longer in cynomolgus and Chinese rhesus macaques than in Indian rhesus macaques. This attenuated pathogenicity was associated with gamma interferon ELISPOT responses to Gag and Env that were generated earlier and of higher frequency in cynomolgus than in Indian rhesus macaques. Cynomolgus macaques also developed higher titer neutralizing antibodies against SHIV-89.6 at 10 and 20 weeks postinoculation than Indian rhesus macaques. These studies demonstrate that the pathogenicity of nonhuman primate lentiviruses varies markedly based on the species or geographic origin of the macaques infected and suggest that the cellular immune responses may contribute to the control of pathogenicity in cynomolgus macaques. While cynomolgus and Chinese rhesus macaques provide alternative animal models of lentiviral infection, the lower levels of viremia in cynomolgus macaques limit the usefulness of infection of this species for vaccine trials that utilize viral load as an experimental endpoint.

* Corresponding author. Mailing address: Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215. Phone: 617-667-4583. Fax: 617-667-8210. E-mail: kreimann{at}bidmc.harvard.edu.

Journal of Virology, July 2005, p. 8878-8885, Vol. 79, No. 14
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.14.8878-8885.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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