Evidence for both intermittent and persistent compartmentalization of HIV-1 in the female genital tract.

HIV-1 has been shown to evolve independently in different anatomical compartments but studies in the female genital tract have been inconclusive. Here we examined evidence of compartmentalization using HIV-1 subtype C envelope (Env) glycoprotein genes (gp160) obtained from matched cervico-vaginal lavage (CVL) and plasma samples over 2-3 years of infection. HIV-1 gp160 amplification from CVL was achieved for only four of 18 acutely infected women and this was associated with the presence of pro-inflammatory cytokines and/or measurable viremia in the CVL. Maximum likelihood trees and divergence analyses showed that all four individuals had monophyletic compartment-specific clusters of CVL and/or plasma-derived gp160 sequences at all or some timepoints. However, two participants (CAP177 and CAP217) had CVL gp160 diversity patterns that differed from those in plasma and showed restricted viral flow from the CVL. Statistical tests of compartmentalization revealed evidence of persistent compartment-specific gp160 evolution in CAP177, while in CAP217 this was intermittent. Lastly, we identified several Env sites that distinguished viruses in these two compartments; for CAP177, amino acid differences arose largely through positive selection while indels were more common in CAP217. In both cases these differences contributed to substantial charge changes spread across the Env. Our data indicates that, in some women, HIV-1 populations within the genital tract can have Env genetic features that differ from those of viruses in plasma: a factor which could potentially impact the sensitivity of viruses in the genital tract to vaginal microbicides and vaccine-elicited antibodies. IMPORTANCE Most HIV-1 infections in sub-Saharan Africa are acquired heterosexually through the genital mucosa. Understanding the properties of viruses replicating in the female genital tract, and whether these properties differ from those of more commonly studied viruses replicating in the blood, is therefore important. Using longitudinal CVL and plasma-derived sequences from four HIV-1 subtype C infected women we found fewer viral migrations from the genital tract to plasma than in the opposite direction, suggesting a mucosal sieve effect from the genital tract to the blood compartment. Evidence for both persistent and intermittent compartmentalization between the genital tract and plasma viruses during chronic infection was detected in two of four individuals; perhaps explaining previously conflicting findings. In cases where compartmentalization occurred, comparison of CVL and plasma-derived HIV sequences indicated that distinct features of viral populations in the CVL may impact the efficacy of microbicides and vaccines designed to provide mucosal immunity.