Adaptive changes after human immunodeficiency virus type 1 transmission: HIV-1 adaptation after transmission

Primary HIV-1 infection (PHI) is associated with a period of viremia, the resolution of which generally coin-cides with the development of both humoral and cellular immune responses. In this study replication-com-petent quasispecies were derived from virus isolated from an individual before and after seroconversion. Viruswas also isolated from the presumed donor. Phenotypic and genotypic analysis of biological clones identifiedtransmission of an R5/M-tropic phenotype. However, the ability of clones derived from the recipient to repli-cate in primary macrophages and PBMCs was restricted after transmission. This apparent selection processwas supported by analysis of molecular clones derived from the isolated virus. Analysis of the ratio of syn-onymous and nonsynonymous substitutions predicted the existence of selective pressure soon after transmis-sion, coincident with the development of HIV-1-specific antibodies. An Env trans-complementation assay dem-onstrated that the infectivity of a clone derived from the recipient after seroconversion was enhanced in thepresence of a selected neutralizing antibody, indicating that the developing humoral immune response may have at least in part contributed to the selective pressure identified.