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Journal of Virology, October 2003, p. 10829-10840, Vol. 77, No. 20
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.20.10829-10840.2003

Early Control of Highly Pathogenic Simian Immunodeficiency Virus/Human Immunodeficiency Virus Chimeric Virus Infections in Rhesus Monkeys Usually Results in Long-Lasting Asymptomatic Clinical Outcomes

Tatsuhiko Igarashi,1 Yasuyuki Endo,1,{dagger} Yoshiaki Nishimura,1 Charles Buckler,1 Reza Sadjadpour,1 Olivia K. Donau,1 Marie-Jeanne Dumaurier,2 Ronald J. Plishka,1 Alicia Buckler-White,1 and Malcolm A. Martin1*

Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892,1 Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York 100212

Received 5 February 2003/ Accepted 14 July 2003

In contrast to simian immunodeficiency viruses (SIVs), which induce immunodeficiency over a 1- to 2-year period, highly pathogenic simian-human immunodeficiency viruses (SHIVs) cause an irreversible and systemic depletion of CD4+ T lymphocytes in macaque monkeys within weeks of inoculation. Nonetheless, the seemingly more aggressive SHIVs have proven to be easier to control by the same vaccine regimens which fail to contain SIV. Because early events during in vivo infections may determine both the pathogenic consequences of the challenge virus and its sensitivity to interventions that prevent disease, we have evaluated the effects of inoculum size and a potent antiretroviral drug on the development of disease in monkeys infected with SHIVDH12R. The results obtained show that in a majority of inoculated animals, suppression of SHIV replication during the first 2 weeks of infection, which prevents complete loss of CD4+ T cells, leads to very low to undetectable postpeak viremia and an asymptomatic clinical course for periods up to 4 years.

* Corresponding author. Mailing address: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 4 Center Dr., Bethesda, MD 20892. Phone: (301) 496-4012. Fax: (301) 402-0226. E-mail: mmartin{at}niaid.nih.gov.

{dagger} Present address: Department of Veterinary Internal Medicine, Faculty of Agriculture, Kagoshima University, 1-21-24 Korimoto, Kagoshima, Kagoshima 890-0065, Japan.

Journal of Virology, October 2003, p. 10829-10840, Vol. 77, No. 20
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.20.10829-10840.2003




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