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Journal of Virology, December 2001, p. 11417-11425, Vol. 75, No. 23
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.23.11417-11425.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Infectious Simian/Human Immunodeficiency Virus with Human Immunodeficiency Virus Type 1 Subtype C from an African Isolate: Rhesus Macaque Model

Thumbi Ndung'u, Yichen Lu, Boris Renjifo, Neal Touzjian, Nicholas Kushner, Victor Pena-Cruz, Vladimir A. Novitsky, Tun-Hou Lee, and Max Essex*

Harvard AIDS Institute and Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts

Received 18 May 2001/Accepted 23 August 2001

Human immunodeficiency virus type 1 (HIV-1) subtype C is responsible for more than 56% of all infections in the HIV and AIDS pandemic. It is the predominant subtype in the rapidly expanding epidemic in southern Africa. To develop a relevant model that would facilitate studies of transmission, pathogenesis, and vaccine development for this subtype, we generated SHIVMJ4, a simian/human immunodeficiency virus (SHIV) chimera based on HIV-1 subtype C. SHIVMJ4 contains the majority of env, the entire second exon of tat, and a partial sequence of the second exon of rev, all derived from a CCR5-tropic, primary isolate envelope clone from southern Africa. SHIVMJ4 replicated efficiently in human, rhesus, and pig-tailed macaque peripheral blood mononuclear cells (PBMCs) in vitro but not in CEMx174 cells. To assess in vivo infectivity, SHIVMJ4 was intravenously inoculated into four rhesus macaques (Macaca mulatta). All four animals became infected as determined through virus isolation, PCR analysis, and viral loads of 107 to 108 copies of viral RNA per ml of plasma during the primary infection phase. We have established a CCR5-tropic SHIVMJ4/rhesus macaque model that may be useful in the studies of HIV-1 subtype C immunology and biology and may also facilitate the evaluation of vaccines to control the spread of HIV-1 subtype C in southern Africa and elsewhere.

* Corresponding author. Mailing address: Immunology and Infectious Diseases Department, Harvard School of Public Health, 651 Huntington Ave., Boston, MA 02115. Phone: (617) 432-0975. Fax: (617) 739-8348. E-mail: messex{at}hsph.harvard.edu.

Journal of Virology, December 2001, p. 11417-11425, Vol. 75, No. 23
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.23.11417-11425.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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