Hemagglutinin Receptor Binding Avidity Drives Influenza A Virus Antigenic Drift

被引：378

作者：

Hensley, Scott E. ^{[1
]}

Das, Suman R. ^{[1
]}

Bailey, Adam L. ^{[1
]}

Schmidt, Loren M. ^{[1
]}

Hickman, Heather D. ^{[1
]}

Jayaraman, Akila ^{[2
,3
]}

Viswanathan, Karthik ^{[2
,3
]}

Raman, Rahul ^{[2
,3
]}

Sasisekharan, Ram ^{[2
,3
]}

Bennink, Jack R. ^{[1
]}

Yewdell, Jonathan W. ^{[1
]}

机构：

[1] NIAID, Viral Dis Lab, Bethesda, MD 20892 USA

[2] MIT, Harvard Mit Div Hlth Sci & Technol, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA

[3] MIT, Dept Biol Engn, Cambridge, MA 02139 USA

来源：

SCIENCE | 2009年 / 326卷 / 5953期

关键词：

VARIANTS; NEUTRALIZATION; RECOGNITION; ANTIBODIES;

D O I：

10.1126/science.1178258

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Rapid antigenic evolution in the influenza A virus hemagglutinin precludes effective vaccination with existing vaccines. To understand this phenomenon, we passaged virus in mice immunized with influenza vaccine. Neutralizing antibodies selected mutants with single-amino acid hemagglutinin substitutions that increased virus binding to cell surface glycan receptors. Passaging these high-avidity binding mutants in naive mice, but not immune mice, selected for additional hemagglutinin substitutions that decreased cellular receptor binding avidity. Analyzing a panel of monoclonal antibody hemagglutinin escape mutants revealed a positive correlation between receptor binding avidity and escape from polyclonal antibodies. We propose that in response to variation in neutralizing antibody pressure between individuals, influenza A virus evolves by adjusting receptor binding avidity via amino acid substitutions throughout the hemagglutinin globular domain, many of which simultaneously alter antigenicity.

引用

页码：734 / 736

页数：3

共 18 条

[1]

Air G M, 1987, Contrib Microbiol Immunol, V8, P20

[2] THE ANTIGENIC STRUCTURE OF THE INFLUENZA-VIRUS A/PR/8/34 HEMAGGLUTININ (H-1 SUBTYPE) [J].