The evolution of human immunodeficiency virus type-1 (HIV-1) envelope molecular properties and coreceptor use at all stages of infection in an HIV-1 donor-recipient pair.

To trace the evolutionary patterns underlying evolution of coreceptor use within a host, we studied an HIV-1 transmission pair involving a donor who exclusively harbored CCR5-using (R5) variants throughout his entire disease course and a recipient who developed CXCR4-using variants. Over time, R5 variants in the donor optimized coreceptor use, which was associated with an increased number of potential N-linked glycosylation sites (PNGS) and elevated V3 charge in the viral envelope. Interestingly, R5 variants that were transmitted to the recipient preserved the viral characteristics of this late stage genotype and phenotype. Following a selective sweep, CXCR4-using variants subsequently emerged in the recipient coinciding with a further increase in the number of PNGS and V3 charge in the envelope of R5 viruses. Although described in a single transmission pair, the transmission and subsequent persistence of R5 variants with late stage characteristics demonstrate the potential for coreceptor use adaptation at the population level.