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

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

Science (New York, N.Y.) (2020-11-21)

Ryan S Roark, Hui Li, Wilton B Williams, Hema Chug, Rosemarie D Mason, Jason Gorman, Shuyi Wang, Fang-Hua Lee, Juliette Rando, Mattia Bonsignori, Kwan-Ki Hwang, Kevin O Saunders, Kevin Wiehe, M Anthony Moody, Peter T Hraber, Kshitij Wagh, Elena E Giorgi, Ronnie M Russell, Frederic Bibollet-Ruche, Weimin Liu, Jesse Connell, Andrew G Smith, Julia DeVoto, Alexander I Murphy, Jessica Smith, Wenge Ding, Chengyan Zhao, Neha Chohan, Maho Okumura, Christina Rosario, Yu Ding, Emily Lindemuth, Anya M Bauer, Katharine J Bar, David Ambrozak, Cara W Chao, Gwo-Yu Chuang, Hui Geng, Bob C Lin, Mark K Louder, Richard Nguyen, Baoshan Zhang, Mark G Lewis, Donald D Raymond, Nicole A Doria-Rose, Chaim A Schramm, Daniel C Douek, Mario Roederer, Thomas B Kepler, Garnett Kelsoe, John R Mascola, Peter D Kwong, Bette T Korber, Stephen C Harrison, Barton F Haynes, Beatrice H Hahn, George M Shaw

PMID33214287

摘要

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.

材料

货号

品牌

产品描述

C2999

Sigma-Aldrich

CryoStor^® 细胞冻存培养基, CS5

220486

Millipore

Chk2 Inhibitor II, Chk2 Inhibitor II, BML-277, CAS 516480-79-8 is a cell-permeable, potent, reversible, ATP-competitive inhibitor of Chk2 (IC₅₀ = 15 nM).