REPEATED EXPOSURE OF RHESUS MACAQUES TO LOW-DOSES OF SIMIAN IMMUNODEFICIENCY VIRUS (SIV) DID NOT PROTECT THEM AGAINST THE CONSEQUENCES OF AHIGH-DOSE SIV CHALLENGE

As part of an in vivo titration study of the macaque simian immunodefi ciency virus (SIVmac) strain 251/spl, macaques were inoculated intrave nously with various dilutions of this infectious SIVmac. Seven animals received dilutions from 10(-3) to 10(-6) of STVmac(251/spl). Two monk eys infected with the 10(-3) dilution of SIVmac exhibited a productive infection as indicated by seroconversion, detection of genomic RNA an d proviral DNA and positive virus isolation. These animals showed a cy totoxic T cell (CTL) response against different SIVmac proteins withou t any measurable T cell proliferation. The five macaques receiving hig her virus dilutions did not seroconvert and were negative for both vir al RNA and for infectious virus, although proviral DNA was detected in their peripheral blood mononuclear cells. In contrast to the animals receiving the 10(-3) virus dilution, these five silently infected monk eys developed an SIV-specific proliferative T cell response but SIV-sp ecific CTL could not be observed. The SIV-specific T cell proliferatio n of the silently infected animals could be boosted by a second low-do se exposure with a 10(-4) or 10(-5) dilution of SIVmac(251/spl). The v irological status of the animals was not changed following this second virus inoculation. Four months later these macaques were challenged i ntravenously with 2 ml of a 10(-4) dilution of SIVmac(251/32H) contain ing 10 monkey ID50. After this challenge all SIV-pre-exposed animals a nd three naive controls became productively infected. In addition, all infected animals developed typical signs of an immunodeficiency withi n 6 months after infection. These observations indicate that macaques infected silently by a low-dose exposure to infectious virus generated a virus-specific cellular immune response. However, SIV-specific T ce ll proliferation alone could not protect the monkeys against an intrav enous challenge with SIVmac and the subsequent development of AIDS-lik e symptoms.