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Focused evolution of HIV-1 neutralizing antibodies revealed by structures and deep sequencing.

Publication ,  Journal Article
Wu, X; Zhou, T; Zhu, J; Zhang, B; Georgiev, I; Wang, C; Chen, X; Longo, NS; Louder, M; McKee, K; O'Dell, S; Perfetto, S; Schmidt, SD; Shi, W ...
Published in: Science
September 16, 2011

Antibody VRC01 is a human immunoglobulin that neutralizes about 90% of HIV-1 isolates. To understand how such broadly neutralizing antibodies develop, we used x-ray crystallography and 454 pyrosequencing to characterize additional VRC01-like antibodies from HIV-1-infected individuals. Crystal structures revealed a convergent mode of binding for diverse antibodies to the same CD4-binding-site epitope. A functional genomics analysis of expressed heavy and light chains revealed common pathways of antibody-heavy chain maturation, confined to the IGHV1-2*02 lineage, involving dozens of somatic changes, and capable of pairing with different light chains. Broadly neutralizing HIV-1 immunity associated with VRC01-like antibodies thus involves the evolution of antibodies to a highly affinity-matured state required to recognize an invariant viral structure, with lineages defined from thousands of sequences providing a genetic roadmap of their development.

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Published In

Science

DOI

EISSN

1095-9203

Publication Date

September 16, 2011

Volume

333

Issue

6049

Start / End Page

1593 / 1602

Location

United States

Related Subject Headings

  • Sequence Analysis, DNA
  • Mutation
  • Molecular Sequence Data
  • Models, Molecular
  • Immunoglobulin Light Chains
  • Immunoglobulin J-Chains
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Fab Fragments
  • Humans
  • High-Throughput Nucleotide Sequencing
 

Citation

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Wu, X., Zhou, T., Zhu, J., Zhang, B., Georgiev, I., Wang, C., … Mascola, J. R. (2011). Focused evolution of HIV-1 neutralizing antibodies revealed by structures and deep sequencing. Science, 333(6049), 1593–1602. https://doi.org/10.1126/science.1207532
Wu, Xueling, Tongqing Zhou, Jiang Zhu, Baoshan Zhang, Ivelin Georgiev, Charlene Wang, Xuejun Chen, et al. “Focused evolution of HIV-1 neutralizing antibodies revealed by structures and deep sequencing.Science 333, no. 6049 (September 16, 2011): 1593–1602. https://doi.org/10.1126/science.1207532.
Wu X, Zhou T, Zhu J, Zhang B, Georgiev I, Wang C, et al. Focused evolution of HIV-1 neutralizing antibodies revealed by structures and deep sequencing. Science. 2011 Sep 16;333(6049):1593–602.
Wu, Xueling, et al. “Focused evolution of HIV-1 neutralizing antibodies revealed by structures and deep sequencing.Science, vol. 333, no. 6049, Sept. 2011, pp. 1593–602. Pubmed, doi:10.1126/science.1207532.
Wu X, Zhou T, Zhu J, Zhang B, Georgiev I, Wang C, Chen X, Longo NS, Louder M, McKee K, O’Dell S, Perfetto S, Schmidt SD, Shi W, Wu L, Yang Y, Yang Z-Y, Yang Z, Zhang Z, Bonsignori M, Crump JA, Kapiga SH, Sam NE, Haynes BF, Simek M, Burton DR, Koff WC, Doria-Rose NA, Connors M, NISC Comparative Sequencing Program, Mullikin JC, Nabel GJ, Roederer M, Shapiro L, Kwong PD, Mascola JR. Focused evolution of HIV-1 neutralizing antibodies revealed by structures and deep sequencing. Science. 2011 Sep 16;333(6049):1593–1602.
Journal cover image

Published In

Science

DOI

EISSN

1095-9203

Publication Date

September 16, 2011

Volume

333

Issue

6049

Start / End Page

1593 / 1602

Location

United States

Related Subject Headings

  • Sequence Analysis, DNA
  • Mutation
  • Molecular Sequence Data
  • Models, Molecular
  • Immunoglobulin Light Chains
  • Immunoglobulin J-Chains
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Fab Fragments
  • Humans
  • High-Throughput Nucleotide Sequencing