Chimeric viruses between SIVmac and various HIV-1 isolates have biological properties that are similar to those of the parental HIV-1

Objective: To examine the biological properties of HIV-1/SIVmac chimeric viruses from HIV-1 isolates that have different replication rates, cell tropisms and cytopathicities. Design and methods: Four chimeric viruses with gag, pol, vif, vpx, nef and long terminal repeats of SIVmac and vpr, tat, rev, vpu and env of various HIV-1 isolates were constructed and compared in vitro. Cynomolgus monkeys were inoculated with two chimeras that were replicative in monkey peripheral blood mononuclear cells (PBMC). Results: The type-specific neutralization of the chimeras by monoclonal antibodies 0.5 beta and mu 5.5, which recognize V3 of HIV-1(IIIB) and HIV-1(MN) respectively, was observed to be similar to those of the parental viruses, HIV-1(NL432), HIV-1(HAN2) and HIV-1(SF13). The chimeras constructed from HIV-1(SF2) and HIV-1(SF13), which were isolates from the same individual hut from different disease stages, reflected their parental properties, that is, the isolate from the later stage was rapid-high replicating, was more cytopathic and had a wider host range. Chimeras constructed from HIV-1(HAN2), HIV-1(SF13) and HIV-1(NL432) were infectious to macaque monkeys, although the monkeys infected with the chimera from HIV-1(SF13) showed lower virus loads and shorter viremic periods than those infected with the others. Conclusions: Chimeras have in vitro properties that are similar to those of their parental HIV-1 isolates, but their growth in macaque PBMC was dependent on which HIV-1 isolate was used. Evaluation of a vaccine by challenging with viruses possessing different antigenicities has become possible in macaque monkeys using newly constructed chimeras.