MACAQUES INFECTED WITH LIVE ATTENUATED SIVMAC ARE PROTECTED AGAINST SUPERINFECTION VIA THE RECTAL MUCOSA

Good protection against systemic challenge in the SIVmac model of AIDS has been provided by prior infection with attenuated virus. To determ ine if such protection extends to intrarectal mucosal challenge two mo lecular clones, SIVmacC8 and SIVmacJ5, were used in this study. SIVmac C8 has an attenuated phenotype in vivo, due to a 12-bp deletion in the nef/3'-LTR, whereas SIVmacJ5 has a full size nef open reading frame a nd induces AIDS in infected macaques. The J5 molecular clone was shown to infect rhesus macaques following atraumatic intrarectal inoculatio n. The dynamics were similar to those following intravenous inoculatio n resulting in early, high, cell-associated viremia and seroconversion . Four macaques previously infected with the attenuated SIVmacC8 resis ted superinfection with SIVmacJ5, following intrarectal inoculation. T hese animals also resisted intrarectal infection with an HIV/SIV chime ric virus (SHIV) composed of SIVmac239 expressing the HXBc2 env, tat, and rev genes, suggesting that immunity to the envelope proteins was u nlikely to be involved in the superinfection resistance. Infection wit h the attenuated SIVmac generated cytotoxic T lymphocytes (CTL) detect able in the peripheral circulation, serum neutralizing antibodies, and SIV-binding antibodies in rectal fluids. SIVmacC8 proviral DNA was fo und in lymph nodes removed at necropsy but there was no evidence for l ocal sequestration of challenge virus. SIV-specific CTL were detected in gut-associated lymph nodes and may have a role in limiting superinf ection following mucosal exposure. (C) 1997 Academic Press.