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AIDS Res Hum Retroviruses. 2017 Dec;33(12):1248-1257. doi: 10.1089/aid.2017.0063. Epub 2017 Oct 17.

A 2-4-Amino Acid Deletion in the V5 Region of HIV-1 Env gp120 Confers Viral Resistance to the Broadly Neutralizing Human Monoclonal Antibody, VRC01.

Author information

1
1 Department of International Health, Kobe University Graduate School of Health Sciences, Kobe University , Kobe, Japan .
2
2 Medical Technology Major, Kobe University School of Medicine Faculty of Health Sciences, School of Medicine, Kobe University , Kobe, Japan .
3
3 Division of Vaccinology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe University , Kobe, Japan .

Abstract

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

PMID:
28903577
DOI:
10.1089/aid.2017.0063
[Indexed for MEDLINE]

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