EMERGENCE OF ANTIGENIC VARIANTS OF SIMIAN IMMUNODEFICIENCY VIRUS (SIVMAC) IN A SERONEGATIVE MACAQUE AFTER SIVMAC239 INFECTION

Infection with the macaque strain of the simian immunodeficiency virus (SIVmac) induces simian immunodeficiency syndrome in rhesus macaques. This report describes the isolation and identification of antigenic v ariants of SIVmac in one of the infected monkeys (macaque #22803). Eig ht naive rhesus monkeys were inoculated with a titered viral stock of the molecularly cloned SIVmac239. Standard serological analysis reveal ed that all but two were seroconverted. Western blot analysis confirme d the seronegativity of macaque #22803. In addition, sera recovered fr om this monkey were not able to neutralize the parent SIVmac239. Howev er, virus could be isolated from all of the infected animals, includin g macaque #22803. Sera recovered were reactive to the autologous virus . The results suggest that the virus from macaque #22803 may have unde rgone extensive antigenic shift in vivo. To test this hypothesis, a po rtion of the gag gene was amplified by the polymerase chain reaction ( PCR), cloned, and sequenced. Sequence analysis revealed amino acid cha nges that were clustered between amino acids 200-245. Evaluation of th e possible selective pressures contributing to the observed viral muta tion revealed that in comparison with the other SIVmac239-infected mon keys, macaque #22803 produced an unusually high T cell proliferative r esponse toward mitogen stimulation before infection, and continued to display a persistently high plasma viremia titer after infection.