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Recapitulation of HIV-1 Env-antibody coevolution in macaques leading to neutralization breadth.

Publication ,  Journal Article
Roark, RS; Li, H; Williams, WB; Chug, H; Mason, RD; Gorman, J; Wang, S; Lee, F-H; Rando, J; Bonsignori, M; Hwang, K-K; Saunders, KO; Wiehe, K ...
Published in: Science
January 8, 2021

Neutralizing antibodies elicited by HIV-1 coevolve with viral envelope proteins (Env) in distinctive patterns, in some cases acquiring substantial breadth. We report that primary HIV-1 envelope proteins-when expressed by simian-human immunodeficiency viruses in rhesus macaques-elicited patterns of Env-antibody coevolution very similar to those in humans, including conserved immunogenetic, structural, and chemical solutions to epitope recognition and precise Env-amino acid substitutions, insertions, and deletions leading to virus persistence. The structure of one rhesus antibody, capable of neutralizing 49% of a 208-strain panel, revealed a V2 apex mode of recognition like that of human broadly neutralizing antibodies (bNAbs) PGT145 and PCT64-35S. Another rhesus antibody bound the CD4 binding site by CD4 mimicry, mirroring human bNAbs 8ANC131, CH235, and VRC01. Virus-antibody coevolution in macaques can thus recapitulate developmental features of human bNAbs, thereby guiding HIV-1 immunogen design.

Duke Scholars

Published In

Science

DOI

EISSN

1095-9203

Publication Date

January 8, 2021

Volume

371

Issue

6525

Location

United States

Related Subject Headings

  • Virus Replication
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Molecular Mimicry
  • Macaca mulatta
  • Humans
  • HIV-1
  • HIV Infections
  • HIV Envelope Protein gp120
  • HIV Antibodies
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Roark, R. S., Li, H., Williams, W. B., Chug, H., Mason, R. D., Gorman, J., … Shaw, G. M. (2021). Recapitulation of HIV-1 Env-antibody coevolution in macaques leading to neutralization breadth. Science, 371(6525). https://doi.org/10.1126/science.abd2638
Journal cover image

Published In

Science

DOI

EISSN

1095-9203

Publication Date

January 8, 2021

Volume

371

Issue

6525

Location

United States

Related Subject Headings

  • Virus Replication
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Molecular Mimicry
  • Macaca mulatta
  • Humans
  • HIV-1
  • HIV Infections
  • HIV Envelope Protein gp120
  • HIV Antibodies