Women infected with clade A human immunodeficiency computer virus type 1 harbor a computer virus population that is genetically diverse in the envelope gene, a fact that contrasts with the homogeneous computer virus populace identified in newly infected men. groups in each of three infected womenQ23, 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 experienced a non-syncytium-inducing phenotype on MT-2 cells and in main 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 usually dominated. The dominant computer virus from Q23 and Q47, but not from Q45, infected a significantly higher quantity 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 VX-702 to CCR5 and gp120, EPSTI1 respectively. These data show that unique envelope genotypes recognized in clade A-infected women near seroconversion confer unique phenotypes that impact viral fitness and that may be due, in part, to different requirements for relative configuration of CD4 and CCR5 on infected cells. Virus transmission from an infected donor to a new host imposes a bottleneck that limits the diversity of the computer virus population. This phenomenon has important implications for human immunodeficiency computer virus type 1 (HIV-1) pathogenesis, because a donor may harbor a computer virus population of up VX-702 to 10% diversity, but the transmission bottleneck may decrease the diversity in a computer virus populace to near-homogeneity (51, 63, 65). In addition to changes in the genotypic diversity of the computer virus population, transmission also affects computer virus phenotype. HIV-1 variants transmitted to a new host are usually macrophage tropic, replicate slowly, are non-syncytium inducing, and utilize CCR5 as a coreceptor (64). As the computer virus populace diversifies in the host, variants acquire different properties that include the capacity to replicate rapidly and induce syncytia in cell lines and to utilize CXCR4 as a coreceptor (53). This phenotypic switch occurs in the majority of infections with clade B HIV-1 and is correlated with disease onset, although clinical symptoms do occur without a switch of viral coreceptor utilization (17). Main isolates that have the capacity to use several coreceptorsdualtropic viruseshave been recognized (11, 25, 54, 55). It is significant that computer virus variants detected over time have both genotypic and phenotypic features that are unique from characteristics of viruses recognized VX-702 at the time of contamination, because this suggests that properties that favor transmission of computer virus between hosts may be distinctive from those that favor replication within a host. Although women represent approximately 50% of HIV-1-infected individuals worldwide, the paradigm for transmission dynamics and viral pathogenesis during the early, asymptomatic years of contamination is based primarily on studies in male cohorts. In contrast to the homogeneous computer virus population found in men, multiple variants were detected in the computer virus population in a cohort of clade A HIV-1-infected women near the time of seroconversion (45). Diversity of the infecting computer virus swarm was related to gender and not to the clade of HIV-1, VX-702 because men from your same region harbored a homogeneous computer virus populace at seroconversion (31). More recently, it has been determined that this gender difference in computer virus diversity between men and women may not relate to differences in diversity in the computer virus inoculum, because close to the time of contamination, viral heterogeneity can be detected in both men and women (29, 31). In men, viral variance is usually rapidly contained and a clonal computer virus populace emerges, whereas computer virus diversity is managed in infected women. The effect of a diverse computer virus populace on prognosis has been debated previously (15, 30, 32, 34, 36, 37, 52, 61). However, the persistence of genetically diverse variants in recently infected women presents a unique opportunity to correlate genetic and biological features and the fate of different viral genotypes transmitted to a naive host, which VX-702 may lead to a better understanding of computer virus characteristics responsible for the successful establishment of new infections. Viral fitness is a parameter that explains the relative ability of a computer virus to produce infectious progeny in a given environment (19). Viruses that replicate more slowly typically produce fewer progeny and consequently have lower fitness than.