Protective immune responses induced by a non-pathogenic simian/human immunodeficiency virus (SHIV) against a challenge of a pathogenic SHIV in monkeys

A simian/human immunodeficiency virus (SHIV)-NM3n containing the human nef, but not the monkey nef, and vpr genes of SIV was inoculated into two cynom olgus monkeys, resulting in systemic infection with a minimum level of tran sient virus load. In order to study the nature of immune responses associat ed with the prevention of a pathogenic SHIV, the SHIV-NM3n-inoculated monke ys and three naive monkeys were intravenously challenged with a pathogenic SHIV containing the envelope gene of HIV-1 89.6. After the heterologous vir us challenge, all of the SHIV-NM3n-inoculated animals completely avoided th e loss of CD4(+) T lymphocytes in PBMC as well as lymphoid tissues compared to pathogenic SHIV-injected control animals. The inhibition of CD4(+) cell depletion was associated with maintaining the proliferative response of he lper T-cells against SIV p27 in the previously nonpathogenic virus-inoculat ed animals following the pathogenic virus challenge. Furthermore, the decli ne of CD28(+) cells, the increase in CD95(+) cells, and the enhancement of in vitro apoptosis in PBMC were inhibited in the non-pathogenic virus-inocu lated animals. These results suggest that nonpathogenic SHIV-NM3n infection induces the protection of monkeys from heterologous pathogenic viruses tha t may be associated with blocking the change in immune responses and the ce ll loss induced by a pathogenic virus.