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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 0.5β and μ5.5, which recognize V3 of HIV-1IIIB and HIV-1MN respectively, was observed to be similar to those of the parental viruses, HIV-1NL432, HIV-1HAN2 and HIV-1SF13. The chimeras constructed from HIV-1SF2 and HIV-1SF13, which were isolates from the same individual but 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-1HAN2, HIV-1SF13 and HIV-1NL432 were infectious to macaque monkeys, although the monkeys infected with the chimera from HIV-1SF13 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.