OCCULT SYSTEMIC INFECTION AND PERSISTENT SIMIAN IMMUNODEFICIENCY VIRUS (SIV)-SPECIFIC CD4(-T-CELL PROLIFERATIVE RESPONSES IN RHESUS MACAQUES THAT WERE TRANSIENTLY VIREMIC AFTER INTRAVAGINAL INOCULATION OF SIV())

The intact cervicovaginal mucosa is a relative barrier to the sexual t ransmission of human immunodeficiency virus type 1 (HIV-1). In the sim ian immunodeficiency virus (SIV) macaque model of HIV infection, seron egative transient viremia (STV; virus isolation positive followed by r epeated negative cultures) occurs after intravaginal inoculation of a low dose of pathogenic SIVmac251 (C. J. Miller, M. Marthas, J. Torten, N, Alexander, J, Moore, G. Doncel, and A. Hendrickx, J. Virol. 68:639 1-6400, 1994). Thirty-one adult female macaques that had been inoculat ed intravaginally with pathogenic SIVmac251 became transiently viremic . One monkey that had been culture negative for a year after SN inocul ation became persistently viremic and developed simian AIDS. No other STV monkey developed persistent viremia or disease, Results of very se nsitive assays showed that 6 of 31 monkeys had weak SIV-specific antib ody responses. SIV-specific antibodies were not detected in the cervic ovaginal secretions of 10 STV monkeys examined. Twenty of 26 monkeys h ad lymphocyte proliferative responses to p(55gag) and/or gp(130env) an tigens; 3 of 6 animals, including the monkey that became persistently viremic, had detectable cytotoxic T-lymphocyte (CTL) responses to SIV. At necropsy, lymphoid tissues and vaginal mucosa were virus culture n egative, but in 10 of 10 animals, SIV provirus was detected by PCR usi ng gag-specific primer pairs, Fifty percent of the PCR-positive tissue samples were also positive for SIV gag RNA by reverse transcriptase P CR, Thus, transient viremia following intravaginal inoculation of path ogenic SIV is associated with persistent, systemic infection, either l atent or very low level productive. Atypical immune responses, charact erized by lymphocyte proliferation and some CTL responses in the absen ce of conventionally detectable antibodies, develop in transiently vir emic monkeys.