Molecular mechanism of resistance to VRC01 neutralization in HIV-1 subtype B′ strains / 中华微生物学和免疫学杂志

ABSTRACT

Objective:To investigate the molecular mechanism of VRC01 resistance in HIV-1 subtype B′ strains isolated from a patient (DRVI01) with broadly neutralizing antibody (bNAb).Methods:Sequences of the HIV-1 subtype B′ strains isolated from patient DRVI01 were compared with those of HIV-1 subtype B′ strains that were isolated at the same time but sensitive to VRC01 antibody. Key amino acids that might affect the neutralization of VRC01 were selected according to literature reports. Effects of the selected amino acids on VRC01 neutralization were verified by site-directed mutation and sequence exchange of membrane proteins from different patients.Results:Single-point mutations of E279D and R282K in LoopD region and N460A and N463Q in V5 region reversed the viral sensitivity to VRC01 neutralization. Combined mutations in two or three above-mentioned sites significantly increased the viral sensitivity to VRC01 antibody compared with single-point mutations. Contrary to literature reports, the glycosylation site mutation of N276 had no influence on the viral sensitivity to VRC01.Conclusions:HIV-1 subtype B′ strains isolated from patient DRV01 with bNAb carried the mutations of D279 and K282 in LoopD region and N460 and N463 in V5 region, resulting in resistance to VRC01 antibody.