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169 An Infectious Simian/Human Immunodeficiency Virus with Human Immunodeficiency Virus Type 1 Subtype C from an African Isolate: Rhesus Macaque Model
T. Ndung'u*, Y. Lu, B. Renjifo, N. Touzjian, N. Kushner, V. Pena-Cruz, V. A. Novitsky, T. H. Lee, and M. Essex
Harvard Univ., Boston, MA, USA
Background: Human immunodeficiency virus type 1 subtype C is now responsible for the majority of infections in the HIV/AIDS pandemic. Although simian/human immunodeficiency virus (SHIV) chimeras have been important for the study of HIV-1 subtype B in rhesus monkeys, no analogous SHIV for HIV-1 subtype C is available for titration in cultured peripheral blood mononuclear cells (PBMCs) of rhesus origin.
Methods: We used standard molecular cloning techniques to generate SHIVMJ4 that contains HIV-1 subtype C env, and partial tat and rev genes, from an African isolate. We assessed whether SHIVMJ4 viruses could replicate in vitro in cells of human, pig-tailed, and rhesus origin. Four rhesus monkeys were then inoculated intravenously with SHIVMJ4, and infection was determined by viral load quantification, PCR, viral isolation, and Western-blot analysis of seroconversion.
Results: We have generated SHIVMJ4, which contains HIV-1 subtype C genes from an African isolate. SHIVMJ4 replicates in cultured rhesus PBMCs and intravenous inoculation of SHIVMJ4 into rhesus macaques resulted in productive infection, with peak HIV-1 RNA plasma loads of 107(108 copies/ml during primary infection.
Conclusions: We have established a rhesus monkey model for HIV-1 subtype C. SHIVMJ4 may facilitate studies of pathogenesis and vaccine development for HIV-1 subtype C.
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