Focused Evolution of HIV-1 Neutralizing Antibodies Revealed by Structures and Deep Sequencing

By Xueling Wu, T. Zhou, Jiang Zhu, Baoshan Zhang, Ivelin S. Georgiev, Charlene Wang, Xuejun Chen, N. Longo, M. Louder, K. McKee and 25 more. Science, 2011

757 citations recorded by the source corpus.

Broadly neutralizing antibodies to HIV with similar specificities can be found in multiple HIV-infected individuals. 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.

Subfields: Ecology, Radiology, Nuclear Medicine and Imaging, Virology

View Paper: https://www.semanticscholar.org/paper/8a1945b0a6eab33f9f8c078002b3e615765c1c9b

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

1. J. Julien
2. P. Klasse
3. R. Sanders
4. G. Ofek
5. A. Yasmeen
6. M. Joyce
7. C. King
8. M. Connors

Citations in the corpus

• A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but Not Non-Neutralizing Antibodies (2013, methodology): “The crystal structure of gp120 in complex with PGV04 (PDB:3SE9; [85]) was fitted into the EM density.”
• Maximum-Entropy Models of Sequenced Immune Repertoires Predict Antigen-Antibody Affinity (2016, neutral): “The experimentally resolved 3D structure of antibody VRC-PG04 in complex with HIV1 gp120 was produced by the authors of [1] it and has been deposited with the Protein Data Bank accession code 3SE9.”
• Developmental Pathway of the MPER-Directed HIV-1-Neutralizing Antibody 10E8 (2016, methodology): “Neutralization was measured using a panel of eight HIV-1 Env-pseudoviruses to infect TZMbl cells as previously described [30] (see S1 Table for details on HIV-1 isolate panel).”