Structural Survey of Broadly Neutralizing Antibodies Targeting the HIV-1 Env Trimer Delineates Epitope Categories and Characteristics of Recognition.

Published

Journal Article

Over the past decade, structures have been determined for broadly neutralizing antibodies that recognize all major exposed surfaces of the prefusion-closed HIV-1-envelope (Env) trimer. To understand this recognition and its implications, we analyzed 206 antibody-HIV-1 Env structures from the Protein Data Bank with resolution suitable to define interaction chemistries and measured antibody neutralization on a 208-strain panel. Those with >25% breadth segregated into almost two dozen classes based on ontogeny and recognition and into six epitope categories based on recognized Env residues. For paratope, the number of protruding loops and level of somatic hypermutation were significantly higher for broad HIV-1 neutralizing antibodies than for a comparison set of non-HIV-1 antibodies (p < 0.0001). For epitope, the number of independent sequence segments was higher (p < 0.0001), as well as the glycan component surface area (p = 0.0005). The unusual characteristics of epitope and paratope delineated here are likely to reflect respectively virus-immune evasion and antibody-recognition solutions that allow effective neutralization of HIV-1.

Full Text

Duke Authors

Cited Authors

  • Chuang, G-Y; Zhou, J; Acharya, P; Rawi, R; Shen, C-H; Sheng, Z; Zhang, B; Zhou, T; Bailer, RT; Dandey, VP; Doria-Rose, NA; Louder, MK; McKee, K; Mascola, JR; Shapiro, L; Kwong, PD

Published Date

  • January 2019

Published In

Volume / Issue

  • 27 / 1

Start / End Page

  • 196 - 206.e6

PubMed ID

  • 30471922

Pubmed Central ID

  • 30471922

Electronic International Standard Serial Number (EISSN)

  • 1878-4186

International Standard Serial Number (ISSN)

  • 0969-2126

Digital Object Identifier (DOI)

  • 10.1016/j.str.2018.10.007

Language

  • eng