The envelope glycoprotein (Env) gp120 of human immunodeficiency virus type 1 (HIV-1) plays a critical role in viral entry into host cells. The broadly neutralizing human monoclonal antibody VRC01, which recognizes the CD4 binding site on gp120, neutralizes more than 90% of HIV-1 isolates. However, some of the CRF01_AE viruses prevalent in Southeast Asia are resistant to VRC01-mediated neutralization. We previously reported that 3 amino acid residues at positions 185, 186, and 197 of gp120 played an important role in the VRC01 resistance of CRF01_AE Env (AE-Env) clones isolated from HIV-infected Thai individuals. However, the VRC01 susceptibility of AE-Env clones was not fully explained by mutations at these 3 residues. In the present study, we examined other factors involved in the acquisition of viral VRC01 resistance. Neutralization tests using lentiviral vectors expressing a series of mutant AE-Env clones revealed that the deletion of 2-4 amino acid residues on the loop structure in the V5 region of gp120 conferred VRC01 resistance to several AE-Env clones. Our results provide novel insights into the mechanisms underlying viral VRC01 resistance.
Keywords: CRF01_AE; HIV-1; V5 region; VRC01; broadly neutralizing antibody; gp120.