Transmission of HIV-1 during Passage through a Bottleneck: Different Evolution of HIV-1 V3 and NEF Quasispecies

Abstract

Early in the AIDS era, it was feared that HIV-1 might evolve into untreatable, pandemic killer strains, similar to the 1918 Influenza outbreak or to today’s MRSA bacterial strains. Epidemiologists wanted urgently to know the origins of HIV-1 and the likelihood of evolution of such strains. HIV-1 exists as quasispecies, and evolution of viral quasispecies is most clearly studied where an external pressure creates a bottleneck through which only some variants survive. We studied variants in hypervariable gene regions characteristic of HIV-1 strains: the V3 domain of env gp120 (the principal neutralizing determinant of HIV-1), and the duplication region of the nef gene (associated with pathogenesis in the host), in two mother-infant pairs after transmission of virus from the mother to her infant, and in nine AIDS patients before and after therapy with didanosine (ddI). Evolutionary drift (accumulation of point mutations) and shift (involving insertion/deletion mutations) to new genotypes were observed in both gene regions, but drift was favored in the V3 region, whereas shift was more prominent in nef. Co-selection of genotypes in env and nef appeared to be unrelated, suggesting the presence of mixed genotypes within natural HIV-1 quasispecies.