Neutralizing epitopes in the membrane-proximal region of HIV-1 gp41: Genetic variability and co-variation

Recent investigations on the passive immunization have proved that neutralizing antibodies directed to the membrane-proximal region of HIV-1 gp41 are potent anti-viral components, so this region is thought to be an attractive target for AIDS vaccine. Three key neutralizing epitopes, ELDKWA (aa662–667), NWFDIT (aa671–676) and ERDRDR (aa739–744) have been mapped in this region. In this study, their genetic variability and co-variation was evaluated. There exists marked shift in the predominant sequence patterns on these three neutralizing epitopes over time. Compared with subtype B, non-B clades exhibit significant genetic variability and co-variation on these three epitopes. Among HIV-1 strains isolated in recent 5 years, about one third displays epitope variants simultaneously on three epitopes. The newly isolated strains with co-variations on several neutralizing epitopes ought to be of strict surveillance in clinical treatment, and those frequent epitope variants should also be considered in vaccine design.