REACTIVATION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-2 IN MACAQUES AFTERSIMIAN IMMUNODEFICIENCY VIRUS SIVMAC SUPERINFECTION

By superinfection of human immunodeficiency virus type 2 (HIV-2) strai n HIV-2ben-infected macaques with simian immunodeficiency virus (SIV) strain SIVmac, we investigated the mutual influences of an apathogenic and a pathogenic virus in vivo. Four rhesus and two cynomolgus monkey s were infected with HIV-2ben in 1988 and 1989, respectively. Virus co uld be reisolated from five of six animals 6 weeks after infection. Th e monkeys remained healthy over the next 2 to 3 years, PCR for viral R NA became negative, and virus could no longer be reisolated by cocultu re. All six macaques were superinfected with the pathogenic SIVmac251/ 32H. Subsequently, five monkeys became persistently viremic, while one animal was protected against the SIVmac infection, In the peripheral blood mononuclear cells and cocultures of the five viremic animals, DN A from both HIV-2 and SIVmac was present. The plasma contained RNA fro m both viruses. Thus, superinfection,vith SIVmac activated HIV-2. A pr oliferative T-cell response against both HIV-2 and (S)IVmac was measur ed in ail animals after superinfection. Such a response was regularly seen after infection with the apathogenic HIV-2 but never when the pat hogenic SIVmac alone was administered. While naive control monkeys ino culated with SIVmac251/32H regularly develop AIDS-like symptoms soon a fter infection and have to be killed, none of the preinfected animals has developed AIDS-like symptoms, but two of six animals developed tum ors. After the SIVmac challenge, however, apoptotic lymphocytes were d etected in the peripheral blood mononuclear cells of all animals. Thus , the presence of an apathogenic viral variant seems to retard the dis ease occurring after infection with a pathogenic virus rather than to confirm total protection. This partial protection appears to depend on a specific proliferative T-cell response early after infection.