Infectivity and immunogenicity of SIVmac/HIV-1 chimeric viruses (SHIVs) with deletions in two or three genes (vpr, nef and vpx).

Two SHIVs with two or three genes deleted (SHIV-drn and SHIV-dxrn) were constructed. The inoculation of monkeys with SHIV-drn resulted in short-term viremia, but inoculation with SHIV-dxrn did not. At 68 weeks post-inoculation, the monkeys were reinoculated with a 100-fold higher dose of each SHIV, but none showed viremia. Killer cell activities against HIV-1 Env were detected in the SHIV-drn- and SHIV-dxrn-inoculated monkeys. Cross-reactive killer activity against HIV-1 Gag and SIVmac Gag was observed in one monkey. Antibodies were not detected in the SHIV-dxrn-inoculated monkeys, but the SHIV-drn-inoculated monkeys showed an anamnestic antibody reaction. These data indicate that SHIV-drn is infectious to and immuno-inducible in macaques but SHIV-dxrn is not.