title: The presence of glutamine at position 315 but not epitope masking predominantly hinders HIV subtype C neutralization by the anti-V3 antibody B4e8.
abstract: Antibody B4e8 exhibits modest cross-neutralizing activity, with preference for HIV subtype B. This preference might be explained by B4e8׳s extensive interaction with Arg315, which occurs at the center of most subtype B V3 sequences but is replaced by Gln in subtype C. The extent to which B4e8׳s ability to neutralize subtype C strains is hindered by Gln315 and/or other factors, e.g. epitope masking, is unclear. We confirmed here that an Arg315-to-Gln substitution in a subtype B virus abrogates B4e8 neutralizing activity. Conversely, B4e8-resistant subtype C viruses were rendered sensitive upon Gln 315-to-Arg substitution. V2 region swapping between B4e8-sensitive and- resistant subtype C strains revealed a role for V2 in limiting B4e8 access, but this was less significant than the absence of Arg315. Our findings, while illustrating the importance of Arg315 for B4e8, suggest that some subtype C strains may be vulnerable to B4e8 derivatives capable of binding stronger to Gln315-containing sequences.
authors: Faculty of Health Sciences, Simon Fraser University, British Columbia, Burnaby, Canada V5A 1S6.
authors: Savrina
authors: S
authors: Manhas
authors: Faculty of Health Sciences, Simon Fraser University, British Columbia, Burnaby, Canada V5A 1S6.
authors: Dennis
authors: D
authors: Chau
authors: Faculty of Health Sciences, Simon Fraser University, British Columbia, Burnaby, Canada V5A 1S6.
authors: Caitlin
authors: C
authors: Rempel
authors: Faculty of Health Sciences, Simon Fraser University, British Columbia, Burnaby, Canada V5A 1S6.
authors: Brenda E
authors: BE
authors: Clark
authors: Faculty of Health Sciences, Simon Fraser University, British Columbia, Burnaby, Canada V5A 1S6.
authors: Kate
authors: K
authors: Auyeung
authors: Faculty of Health Sciences, Simon Fraser University, British Columbia, Burnaby, Canada V5A 1S6; Department of Molecular Biology and Biochemistry, Simon Fraser University, British Columbia, Burnaby, Canada V5A 1S6. Electronic address: rpantophlet@sfu.ca.
authors: Ralph
authors: R
authors: Pantophlet
mesh_terms: D019943:Amino Acid Substitution; D057134:Antibodies, Neutralizing / Q000276:immunology*; D001120:Arginine / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D005973:Glutamine / Q000276:immunology*; D015483:HIV Antibodies / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000939:Epitopes; D015483:HIV Antibodies; D054299:env Gene Products, Human Immunodeficiency Virus; D005973:Glutamine; D001120:Arginine
keywords: Angle of interaction; Arg315; Neutralizing antibody; Subtype C; V2 region; V3 masking