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

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Abstract
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 SHIV MJ4 , a simian/human immunodeficiency virus (SHIV) chimera based on HIV-1 subtype C. SHIV MJ4 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. SHIV MJ4 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, SHIV MJ4 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 10 7 to 10 8 copies of viral RNA per ml of plasma during the primary infection phase. We have established a CCR5-tropic SHIV MJ4 /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.