A Site of Vulnerability on the Influenza Virus Hemagglutinin Head Domain Trimer Interface

被引：179

作者：

Bangaru, Sandhya ^{[1
]}

Lang, Shanshan ^{[2
]}

Schotsaert, Michael ^{[3
,6
]}

Vanderven, Hillary A. ^{[4
]}

Zhu, Xueyong ^{[2
]}

Kose, Nurgun ^{[5
]}

Bombardi, Robin ^{[5
]}

Finn, Jessica A. ^{[1
]}

Kent, Stephen J. ^{[4
]}

Gilchuk, Pavlo ^{[5
]}

Gilchuk, Iuliia ^{[5
]}

Turner, Hannah L. ^{[2
]}

Garcia-Sastre, Adolfo ^{[3
,6
,7
]}

Li, Sheng ^{[8
]}

Ward, Andrew B. ^{[2
]}

Wilson, Ian A. ^{[2
,9
]}

Crowe, James E., Jr. ^{[1
,5
,10
]}

机构：

[1] Vanderbilt Univ, Med Ctr, Dept Pathol Microbiol & Immunol, Nashville, TN 37232 USA

[2] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA

[3] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA

[4] Univ Melbourne, Peter Doherty Inst Infect & Immun, Dept Microbiol & Immunol, Melbourne, Vic, Australia

[5] Vanderbilt Univ, Vanderbilt Vaccine Ctr, Med Ctr, Nashville, TN 37232 USA

[6] Icahn Sch Med Mt Sinai, Global Hlth & Emerging Pathogens Inst, New York, NY 10029 USA

[7] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA

[8] Univ Calif San Diego, Sch Med, Dept Med & Biomed Sci, La Jolla, CA 92093 USA

[9] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA

[10] Vanderbilt Univ, Dept Pediat, Med Ctr, Nashville, TN 37232 USA

来源：

CELL | 2019年 / 177卷 / 05期

关键词：

RECEPTOR-BINDING SITE; BROADLY NEUTRALIZING ANTIBODY; STRUCTURAL INSIGHTS; ANTIGENIC STRUCTURE; MASS-SPECTROMETRY; HIV-1; ENV; VACCINE; EPITOPE; RECOGNITION; EXCHANGE;

D O I：

10.1016/j.cell.2019.04.011

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Here, we describe the discovery of a naturally occurring human antibody (Ab), FluA-20, that recognizes a new site of vulnerability on the hemagglutinin (HA) head domain and reacts with most influenza A viruses. Structural characterization of FluA-20 with H1 and H3 head domains revealed a novel epitope in the HA trimer interface, suggesting previously unrecognized dynamic features of the trimeric HA protein. The critical HA residues recognized by FluA-20 remain conserved across most subtypes of influenza A viruses, which explains the Ab's extraordinary breadth. The Ab rapidly disrupted the integrity of HA protein trimers, inhibited cell-to-cell spread of virus in culture, and protected mice against challenge with viruses of H1N1, H3N2, H5N1, or H7N9 subtypes when used as prophylaxis or therapy. The FluA-20 Ab has uncovered an exceedingly conserved protective determinant in the influenza HA head domain trimer interface that is an unexpected new target for anti-influenza therapeutics and vaccines.

引用

页码：1136 / +

页数：35

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