Examination of HIV evolution in response to host pressures

The overarching aim of this thesis was to study the evolution of HIV-1 in response to host pressures. The main data chapter comprises a detailed HIV-1 transmission study where we identified a putative case of X4 HIV-1 transmission from a CCR5-wt/wt donor to a recipient homozygous for the naturally-occurring 32 base pair deletion in the CCR5 gene (CCR5-∆32/∆32). This rare genotype confers resistance to infection by CCR5-using (“R5”) HIV-1 strains not CXCR4-using (“X4”) strains. Using ultradeep sequencing and phylogenetic analysis, we estimate the number of founder viruses that established infection in both donor and recipient (one in each case), reconstruct their sequences, and study within-host HIV-1 evolution and coreceptor usage. Notably, results suggest that HIV-1 infection in the recipient was initiated by transfer of an infected cell (i.e. not a virion) from the donor, and reveal differential HIV-1 evolution in both members of the pair.