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猕猴中HIV-1病毒抗体共同进化
作者:小柯机器人 发布时间:2020/11/22 23:29:15

美国宾夕法尼亚大学George M. Shaw研究组取得最新进展。他们的最新研究进行了猕猴中HIV-1 病毒包膜蛋白(Env)抗体共同进化导致中和广度的概述。相关论文发表在2020年11月19日出版的《科学》杂志上。

他们报道当猿猴-人免疫缺陷病毒在猕猴中表达时,主要的HIV-1包膜蛋白引起的Env-抗体协同进化模式与人类中的相似。这包括用于表位识别的保守的免疫遗传、结构和化学解决方案,以及精确的Env-am肌苷酸替代、插入和缺失,从而导致病毒持续存在。能够中和208株菌株中的49%。

一种恒河猴抗体的结构揭示了V2顶点识别模式,类似于人bNAbs PGT145 / PCT64-35S。 另一种恒河猴抗体通过CD4模仿人类bNAb 8ANC131 / CH235 / VRC01的方式结合CD4结合位点。因此,猕猴中的病毒抗体共同进化可以概括人类bNAb的发育特征,从而指导HIV-1免疫原设计。

据悉,HIV-1引发的中和抗体与Env以独特的方式共同进化,在某些情况下获得了广泛的传播。

附:英文原文

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

Author: 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 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

Issue&Volume: 2020/11/19

Abstract: 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 strikingly similar to those in humans. This included conserved immunogenetic, structural and chemical solutions to epitope recognition and precise Env-am ino 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 bNAbs PGT145/PCT64-35S. Another rhesus antibody bound the CD4-binding site by CD4 mimicry mirroring human bNAbs 8ANC131/CH235/VRC01. Virus-antibody coevolution in macaques can thus recapitulate developmental features of human bNAbs, thereby guiding HIV-1 immunogen design.

DOI: 10.1126/science.abd2638

Source: https://science.sciencemag.org/content/early/2020/11/18/science.abd2638

期刊信息
Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037