Effect of the maturation of neutralizing antibodies on human immunodeficiency virus (HIV) envelope evolution in HIV-infected subjects.

Delineating the course of NAb (neutralizing antibody) development in natural infection may provide clues for NAb-targeted HIV-1 vaccine design. Two subjects, A (non-neutralizer) and E (neutralizer), were chosen from 75 HIV-1 positive subjects of a MSM (men who have sex with men) cohort to investigate the key events of virus evolution in the development course of neutralizing antibodies. Pseudovirus quasispecies (at least 10 strains) were generated for each time points of the infection course. The diversity and divergence of the env quasispecies per time point for subject E were significantly higher than those for subject A (p<0.05). Compared with subject A, the gp160 derived from subject E acquired longer V1V2 region and more N-glycans during the development of neutralizing antibodies. The developing course of neutralizing antibody lagged behind the virus evolution, of which the pseudoviruses could only been neutralized by the latter time-point sera. The neutralization-driven evolution of the virus for subject E was mostly mapped to the C1-C3 region of gp160. Through site-directed mutagenesis, some key sites and region were identified to be associated with the virus escape, including: Q85P, H183P, K340E, L365S, L369I, I372V and insertions of 355N in C3 and NITDEVKIG in V1 region.