Design and Structure of an Engineered Disulfide-Stabilized Influenza Virus Hemagglutinin Trimer

被引：34

作者：

Lee, Peter S. ^{[1
,2
]}

Zhu, Xueyong ^{[1
]}

Yu, Wenli ^{[1
]}

Wilson, Ian A. ^{[1
,2
]}

机构：

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

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

来源：

JOURNAL OF VIROLOGY | 2015年 / 89卷 / 14期

关键词：

ANTIBODY RECOGNITION; GLYCOPROTEIN; IMMUNOGEN; EPITOPES; BINDING; ORIGIN; DOMAIN; MICE;

D O I：

10.1128/JVI.00808-15

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

We engineered a disulfide-stabilized influenza virus hemagglutinin (HA) trimer, termed HA3-SS, by introducing cysteine residues into the HA stem to covalently bridge the three protomers. HA3-SS has increased thermostability compared to wild-type HA, and binding of head-and stem-targeted antibodies (Abs) is preserved; only minor structural changes are found in the vicinity of the additional disulfide. This platform has been applied to H1 and H3 HAs and provides prospects for design of intact, stabilized influenza virus HA immunogens.

引用

页码：7417 / 7420

页数：4

共 30 条

[1] Design of Escherichia coli-Expressed Stalk Domain Immunogens of H1N1 Hemagglutinin That Protect Mice from Lethal Challenge [J].

Bommakanti, Gayathri ;

Lu, Xianghan ;

Citron, Michael P. ;

Najar, Tariq Ahmad ;

Heidecker, Gwendolyn J. ;

ter Meulen, Jan ;

Varadarajan, Raghavan ;

Liang, Xiaoping .

JOURNAL OF VIROLOGY, 2012, 86 (24) :13434-13444

[2] Design of an HA2-based Escherichia coli expressed influenza immunogen that protects mice from pathogenic challenge [J].

Bommakanti, Gayathri ;

Citron, Michael P. ;

Hepler, Robert W. ;

Callahan, Cheryl ;

Heidecker, Gwendolyn J. ;

Najar, Tariq Ahmad ;

Lu, Xianghan ;

Joyce, Joseph G. ;

Shiver, John W. ;

Casimiro, Danilo R. ;

ter Meulen, Jan ;

Liang, Xiaoping ;

Varadarajan, Raghavan .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (31) :13701-13706

[3] Mechanisms of Hemagglutinin Targeted Influenza Virus Neutralization [J].

Brandenburg, Boerries ;

Koudstaal, Wouter ;

Goudsmit, Jaap ;

Klaren, Vincent ;

Tang, Chan ;

Bujny, Miriam V. ;

Korse, Hans J. W. M. ;

Kwaks, Ted ;

Otterstrom, Jason J. ;

Juraszek, Jarek ;

van Oijen, Antoine M. ;

Vogels, Ronald ;

Friesen, Robert H. E. .

PLOS ONE, 2013, 8 (12)

[4] STRUCTURE OF INFLUENZA HEMAGGLUTININ AT THE PH OF MEMBRANE-FUSION [J].

BULLOUGH, PA ;

HUGHSON, FM ;

SKEHEL, JJ ;

WILEY, DC .

NATURE, 1994, 371 (6492) :37-43

[5] Broadly Neutralizing Antiviral Antibodies [J].

Corti, Davide ;

Lanzavecchia, Antonio .

ANNUAL REVIEW OF IMMUNOLOGY, VOL 31, 2013, 31 :705-742

[6] Highly Conserved Protective Epitopes on Influenza B Viruses [J].

Dreyfus, Cyrille ;

Laursen, Nick S. ;

Kwaks, Ted ;

Zuijdgeest, David ;

Khayat, Reza ;

Ekiert, Damian C. ;

Lee, Jeong Hyun ;

Metlagel, Zoltan ;

Bujny, Miriam V. ;

Jongeneelen, Mandy ;

van der Vlugt, Remko ;

Lamrani, Mohammed ;

Korse, Hans J. W. M. ;

Geelen, Eric ;

Sahin, Ozcan ;

Sieuwerts, Martijn ;

Brakenhoff, Just P. J. ;

Vogels, Ronald ;

Li, Olive T. W. ;

Poon, Leo L. M. ;

Peiris, Malik ;

Koudstaal, Wouter ;

Ward, Andrew B. ;

Wilson, Ian A. ;

Goudsmit, Jaap ;

Friesen, Robert H. E. .

SCIENCE, 2012, 337 (6100) :1343-1348

[7] Cross-neutralization of influenza A viruses mediated by a single antibody loop [J].

Ekiert, Damian C. ;

Kashyap, Arun K. ;

Steel, John ;

Rubrum, Adam ;

Bhabha, Gira ;

Khayat, Reza ;

Lee, Jeong Hyun ;

Dillon, Michael A. ;

O'Neil, Ryann E. ;

Faynboym, Aleksandr M. ;

Horowitz, Michael ;

Horowitz, Lawrence ;

Ward, Andrew B. ;

Palese, Peter ;

Webby, Richard ;

Lerner, Richard A. ;

Bhatt, Ramesh R. ;

Wilson, Ian A. .

NATURE, 2012, 489 (7417) :526-+

[8] A Highly Conserved Neutralizing Epitope on Group 2 Influenza A Viruses [J].

Ekiert, Damian C. ;

Friesen, Robert H. E. ;

Bhabha, Gira ;

Kwaks, Ted ;

Jongeneelen, Mandy ;

Yu, Wenli ;

Ophorst, Carla ;

Cox, Freek ;

Korse, Hans J. W. M. ;

Brandenburg, Boerries ;

Vogels, Ronald ;

Brakenhoff, Just P. J. ;

Kompier, Ronald ;

Koldijk, Martin H. ;

Cornelissen, Lisette A. H. M. ;

Poon, Leo L. M. ;

Peiris, Malik ;

Koudstaal, Wouter ;

Wilson, Ian A. ;

Goudsmit, Jaap .

SCIENCE, 2011, 333 (6044) :843-850

[9] Antibody Recognition of a Highly Conserved Influenza Virus Epitope [J].

Ekiert, Damian C. ;

Bhabha, Gira ;

Elsliger, Marc-Andre ;

Friesen, Robert H. E. ;

Jongeneelen, Mandy ;

Throsby, Mark ;

Goudsmit, Jaap ;

Wilson, Ian A. .

SCIENCE, 2009, 324 (5924) :246-251

[10] Antigenic stability of H1N1 pandemic vaccines correlates with vaccine strain [J].

Farnsworth, Aaron ;

Cyr, Terry D. ;

Li, Changgui ;

Wang, Junzhi ;

Li, Xuguang .

VACCINE, 2011, 29 (08) :1529-1533

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