Longitudinal Analysis of HIV Type 1 Subtype C Envelope Sequences from South Africa

Abstract

The envelope genes of 23 subtype C viral isolates from five individuals with early HIV-1 infection, followed for 2-4 years, were sequenced, analyzed, and correlated to coreceptor usage. Isolates from three participants used the CCR5 coreceptor at all time points, with no significant adaptations in the variable loop lengths, predicted N-linked glycosylation sites, or predicted change in sensitivity to monoclonal antibodies with disease progression. However, two individuals, Du151 and Du179, who had previously been shown to be dually infected with two phylogenetically distinct subtype C strains, were able to use CXCR4 with disease progression. The intraperson genetic diversity was 9% for Du151 and 3% for Du179 compared to <2% for participants who did not undergo a coreceptor switch. In both cases this coreceptor switch was associated with specific amino acid changes in the crown, an increased net amino acid charge in the V3 loop, and an increase in the length of the V1 region.