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.