Differences of cytotoxic T-lymphocyte pressure and divergent evolution of several CRF07_BC clusters circulating in men who have sex with men in China

Abstract

The HIV-1 CRF07_BC strain is now the major recombinant form in China among the population of men who have sex with men (MSM), and has critically contributed to the HIV-1 epidemic in recent years. The phylodynamic and virological differences among CRF07_BC clusters circulating in MSM, and the factors that could be driving their evolution, remains unclear. Using the HIV-1 CRF07_BC strains obtained from the Los Alamos HIV database, we undertook a large-scale phylogenetic analysis using the maximum likelihood method of partial gag, pol, and env segments to infer their evolutionary relationships. The demographic histories of clusters were determined using the Bayesian Markov chain Monte Carlo (MCMC) method. For four pol clusters we analyzed the non-synonymous (dN) to synonymous (dS) substitution rates and performed site to site analysis to identify positive selection sites and cytotoxic T-lymphocyte (CTL) escape mutation positions. MSM was found to be the predominant risk factor for all four of the CRF07_BC epidemic pol segment clusters with the largest number of infections. Two of those clusters had higher growth in the effective number of infections, and two clusters had slower growth. Analysis of all four clusters showed no significant differences in the mean substitution rates and dN/dS selection pressure ratios. However, a site to site codon analysis found thirteen significant positive selection sites. Ten of these sites are CTL escape mutations. The two clusters with the higher growth in infections had seven and eight pol segment CTL escape mutation sites respectively, while the two with slower growth had only one or two. Our findings demonstrated differences in the CTL escape mutation and divergent evolution of several CRF07_BC clusters circulating among men who have sex with men in China.