Molecular epidemiology of genital Chlamydia trachomatis infection in high-risk women in Senegal, West Africa.

The prevalence and heterogeneity of Chlamydia trachomatis infections in a cohort of female sex workers in Dakar (Senegal) were determined by using endocervical-swab-based PCR DNA amplification assays. The overall prevalence of cervical chlamydial infection was 28.5% (206 of 722), and most of these infections were asymptomatic. An increased number of sexual partners was significantly associated with infection (adjusted odds ratio [AOR] = 1.37; 95% confidence interval [CI] = 1.06 to 1.77), while the presence of a yeast infection was negatively associated with chlamydial infection (AOR = 0.28; 95% CI = 0.10 to 0.83). Six different C. trachomatis genotypes were identified based on phylogenetic analysis of the omp1 gene sequences. Interestingly, genotype E predominated (47.6%) and was not associated with visible signs of cervical inflammation compared to non-E genotypes (P < 0.05). Overall, the high rate of asymptomatic C. trachomatis infection by genotype E may suggest genotype-specific properties that confer a transmission advantage in this high risk population.

CCR5 coreceptor utilization involves a highly conserved arginine residue of HIV type 1 gp120.

The seven-transmembrane CCR5 was recently found to double as a coreceptor for a genetically diverse family of human and nonhuman primate lentiviruses. Paradoxically, the main region of the envelope protein believed to be involved in CCR5 utilization was mapped to hypervariable region 3, or V3, of the envelope glycoprotein gp120. In this study, we addressed the question of whether functional convergence in CCR5 utilization is mediated by certain V3 residues that are highly conserved among HIV type 1 (HIV-1), HIV type 2, and simian immunodeficiency virus. Site-directed mutagenesis carried out on three such V3 residues revealed that the Arg-298 of HIV-1 gp120 has an important role in CCR5 utilization. In contrast, no effect was observed for the other residues we tested. The inability of Arg-298 mutants to use CCR5 was not attributed to global alteration of gp120 conformation. Neither the expression, processing, and incorporation of mutant envelope proteins into virions, nor CD4 binding were significantly affected by the mutations. This interpretation is further supported by the finding that alanine substitutions of five residues immediately adjacent to the arginine residue had no effect on CCR5 utilization. Taken together, our data strongly suggests that the highly conserved Arg-298 residue identified in the V3 of HIV-1 has a significant role in CCR5 utilization, and may represent an unusually conserved target for future anti-viral designs.

Pattern of gp120 sequence divergence linked to a lack of clinical progression in human immunodeficiency virus type 1 infection.

Differential rates of AIDS development and/or T4 lymphocyte depletion in HIV-1-infected individuals remain unexplained. The hypothesis that qualitative differences in selection pressure in vivo may account for different rates of disease progression was addressed in nine eligible study participants from a cohort of 315 homosexual men who have been followed since 1985. Disproportionately fewer changes in variable regions and more in C3 of gp12O were found to be significantly associated with slower disease progression. Our finding provides the first example to demonstrate that differential selection pressure related to the emergence of HIV-1 variants is associated with long term nonprogression. Candidate vaccines that elicit strong selection pressure on C3 of gp120 are likely to provide better protection than those targeting variable regions.