AEGiS-14IAC: Rhesus macaque model of simian-human immunodeficiency virus containing human immunodeficiency virus type 1 subtype C genes: in vitro titration, persistent infection but control of viremia upon one-year follow-up.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Rhesus macaque model of simian-human immunodeficiency virus containing human immunodeficiency virus type 1 subtype C genes: in vitro titration, persistent infection but control of viremia upon one-year follow-up.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. A10053)

Ndung'u T, Lu Y, Renjifo B, Touzjian N, Kushner N, Pena-Cruz V, Novitsky VA, Lee TH, Essex M
Harvard University, Boston, United States

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 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 four rhesus macaques resulted in productive infection, with peak HIV-1 RNA plasma loads of 107-108 copies/ml during primary infection. The animals were able to control viremia at below 103 copies/ml, CD4 counts remained steady, but virus can still be isolated from them one year after 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. In vivo passage may be necessary to render SHIVMJ4 pathogenic for experiments where this property is needed.

Keywords: AEGIS, HIV-1, Viremia, Macaca mulatta, Viral Load, CD4 Lymphocyte Count, Genes, rev, HIV Infections, Acquired Immunodeficiency Syndrome, Simian Acquired Immunodeficiency Syndrome, Animal, Human, In Vitro, genetics

020707
A10053