Functional consequences of mutations in HIV-1 Gag p55 selected by CTL pressure

Amino acid changes in the CA domain of the p55 Gag protein of HIV-1 have been observed during the course of an infection that appear to correlate with escape from cytotoxic T cell surveillance (Phillips et al., Nature 354, 453-459, 1991). A corollary of this observation is that all such changes should be functionally silent but, as the changes were observed in populations of virus, this has not been formally demonstrated. We have introduced the amino acid changes representative of those observed to occur in vivo into the Gag p55 gene cloned in the baculovirus expression system where the wild-type gene product produces virus-like particles (VLP). We show that none of these mutations affect particle formation as judged by VLP morphology and density despite their location within a sequence of the Gag open reading frame known to be important for assembly. These data add tacit support to the hypothesis that CTL pressure can drive virus evolution in HIV and add to the fine mapping of sequences involved in Gag subunit interactions.