Envelope Variants from Women Recently Infected with Clade A Human Immunodeficiency Virus Type 1 Confer Distinct Phenotypes That Are Discerned by Competition and Neutralization Experiments

Women infected with clade A human immunodeficiency virus type 1 harbor a virus population that is genetically diverse in the envelope gene, a fact that contrasts with the homogeneous virus population identified in newly infected men. It is not known whether viral genetic diversity at this early stage of infection is manifested as phenotypic diversity. This is a significant question because phenotypic diversity in the viral population that establishes infection in women may have important implications for pathogenesis and therapeutic intervention. Thus, in this study we compared the biological properties of three pairs of chimeric viruses that contained envelope genes representative of variant groups in each of three infected women-Q23, Q45, and Q47. Envelope chimeras were evaluated for replication in stimulated and resting peripheral blood mononuclear cells alone and in competition, for coreceptor use, and for neutralization sensitivity. All viruses utilized CCR5 exclusively and had a non-syncytium-inducing phenotype on MT-2 cells and in primary culture. There were no significant differences in replication parameters between paired variants in individual cultures. However, in competition experiments, one chimera of each variant pair always dominated. The dominant virus from Q23 and Q47, but not from Q45, infected a significantly higher number of CCR5- and CD4-expressing GHOST cells than the weaker chimeras. Significantly, chimeric viruses from Q47 and Q45 showed markedly different neutralization sensitivity to antibodies to CCR5 and gp120, respectively. These data indicate that distinct envelope genotypes identified in clade A-infected women near seroconversion confer unique phenotypes that affect viral fitness and that may be due, in part, to different requirements for relative configuration of CD4 and CCR5 on infected cells.