title: Specific sequences commonly found in the V3 domain of HIV-1 subtype C isolates affect the overall conformation of native Env and induce a neutralization-resistant phenotype independent of V1/V2 masking.
abstract: Primary HIV-1 isolates are relatively resistant to neutralization by antibodies commonly induced after infection or vaccination. This is generally attributed to masking of sensitive epitopes by the V1/V2 domain and/or glycans situated at various positions in Env. Here we identified a novel masking effect mediated by subtype C-specific V3 sequences that contributes to the V1/V2-independent and glycan-independent neutralization resistance of chimeric and primary Envs to antibodies directed against multiple neutralization domains. Positions at several conserved charged and hydrophobic sites in the V3 crown and stem were also shown to affect neutralization phenotype. These results indicated that substitutions typically present in subtype C and related V3 sequences influence the overall conformation of native Env in a way that occludes multiple neutralization targets located both within and outside of the V3 domain, and may reflect an alternative mechanism for neutralization resistance that is particularly active in subtype C and related isolates.
authors: Public Health Research Institute Center, Rutgers University, 225 Warren Street, Newark, NJ 07103, USA.
authors: Aidy
authors: A
authors: Salomon
authors: Chavdar
authors: C
authors: Krachmarov
authors: Zhong
authors: Z
authors: Lai
authors: William
authors: W
authors: Honnen
authors: Barry S
authors: BS
authors: Zingman
authors: Julie
authors: J
authors: Sarlo
authors: Miroslaw K
authors: MK
authors: Gorny
authors: Susan
authors: S
authors: Zolla-Pazner
authors: James E
authors: JE
authors: Robinson
authors: Abraham
authors: A
authors: Pinter
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D011487:Protein Conformation; D016415:Sequence Alignment; D054299:env Gene Products, Human Immunodeficiency Virus / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D015483:HIV Antibodies; D054299:env Gene Products, Human Immunodeficiency Virus
keywords: Conformational effect; Epitope masking; HIV-1; Subtype C; V3 domain