Infectious simian/human immunodeficiency virus with human immunodeficiencyvirus type 1 subtype C from an African isolate: Rhesus macaque model

Human immunodeficiency virus type 1 (HIV-1) subtype C is responsible for mo re than 56% of all infections in the HIV and AIDS pandemic. It is the predo minant subtype in the rapidly expanding epidemic in southern Africa. To dev elop a relevant model that would facilitate studies of transmission, pathog enesis, and vaccine development for this subtype, we generated SHIVMJ4, a s imian/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 e fficiently in human, rhesus, and pig-tailed macaque peripheral blood mononu clear cells (PBMCs) in vitro but not in CEMx174 cells. To assess in vivo in fectivity, SHIVMJ4 was intravenously inoculated into four rhesus macaques ( Macaca mulatta). All four animals became infected as determined through vir us isolation, PCR analysis, and viral loads of 10(7) to 10(8) copies of vir al RNA per ml of plasma during the primary infection phase. We have establi shed a CCR5-tropic SHIVMJ4/rhesus macaque model that may be useful in the s tudies of HIV-1 subtype C immunology and biology and may also facilitate th e evaluation of vaccines to control the spread of HIV-1 subtype C in southe rn Africa and elsewhere.