Immunodeficiency Virus Type 1 Women Infected with Clade A Human Genital Tract and Peripheral Blood of Evolution of Envelope Sequences from the

The development of viral diversity during the course of human immunodeficiency virus type 1 (HIV-1) in-fection may significantly influence viral pathogenesis. The paradigm for HIV-1 evolution is based primarily onstudies of male cohorts in which individuals were presumably infected with a single virus variant of subtypeB HIV-1. In this study, we evaluated virus evolution based on sequence information of the V1, V2, and V3portions of HIV-1 clade A envelope genes obtained from peripheral blood and cervical secretions of threewomen with genetically heterogeneous viral populations near seroconversion. At the first sample following sero-conversion, the number of nonsynonymous substitutions per potential nonsynonymous site (dn) significantlyexceeded substitutions at potential synonymous sites (ds) in plasma viral sequences from all individuals. Gen-erally, values of dn remained higher than values of ds as sequences from blood or mucosa evolved. Mutationsaffected each of the three variable regions of the envelope gene differently; insertions and deletions dominatedchanges in V1, substitutions involving charged amino acids occurred in V2, and sequential replacement ofamino acids over time at a small subset of positions distinguished V3. The relationship among envelopenucleotide sequences obtained from peripheral blood mononuclear cells, plasma, and cervical secretions wasevaluated for each individual by both phylogenetic and phenetic analyses. In all subjects, sequences fromwithin each tissue compartment were more closely related to each other than to sequences from other tissues(phylogenetic tissue compartmentalization). At time points after seroconversion in two individuals, there wasalso greater genetic identity among sequences from the same tissue compartment than among sequences fromdifferent tissue compartments (phenetic tissue compartmentalization). Over time, temporal phylogenetic andphenetic structure was detectable in mucosal and plasma viral samples from all three women, suggesting acontinual process of migration of one or a few infected cells into each compartment followed by localizedexpansion and evolution of that population.