IN-VIVO REPLICATION CAPACITY RATHER THAN IN-VITRO MACROPHAGE TROPISM PREDICTS EFFICIENCY OF VAGINAL TRANSMISSION OF SIMIAN IMMUNODEFICIENCYVIRUS OR SIMIAN HUMAN IMMUNODEFICIENCY VIRUS IN RHESUS MACAQUES/

We used the rhesus macaque model of heterosexual human immunodeficienc y virus (HIV) transmission to test the hypothesis that in vitro measur es of macrophage tropism predict the ability of a primate lentivirus t o initiate a systemic infection after intravaginal inoculation. A sing le atraumatic intravaginal inoculation with a T-cell-tropic molecular clone of simian immunodeficiency virus (SIV), SIVmac239, or a dualtrop ic recombinant molecular clone of SIV, SIVmac239/1A11/239, or uncloned dualtropic SIVmac251 or uncloned dualtropic simian/human immunodefici ency virus (SHIV) 89.6-PD produced systemic infection in all rhesus ma caques tested, However, vaginal inoculation with a dualtropic molecula r clone of SIV, SIVmac1A11, resulted in transient viremia in one of tw o rhesus macaques. It has previously been shown that 12 intravaginal i noculations with SIVmac1A11 resulted in infection of one of five rhesu s macaques (M. L. Marthas, C. J. Miller, S. Sutjipto, J. Higgins, J. T orten, B. L. Lohman, R. E. Unger, H. Kiyono, J. R. McGhee, P. A. Marx, and N. C. Pedersen, J. Med. Primatol. 21:99-107, 1992), In addition, SHIV HXBc2, which replicates in monkey macrophages, does not infect rh esus macaques following multiple vaginal inoculations, while T-cell-tr opic SHIV 89.6 does (Y. Lu, P. B. Brosio, M. Lafaile, J. Li, R. S. Col lman, J. Sodroski, and C. J. Miller, J. Virol. 70:3045-3050, 1996). Th ese results demonstrate that in vitro measures of macrophage tropism d o not predict if a SIV or SHIV will produce systemic infection after i ntravaginal inoculation of rhesus macaques. However, we did find that the level to which these viruses replicate in vivo after intravenous i noculation predicts the outcome of intravaginal inoculation with each virus.