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
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
收藏
页码:7417 / 7420
页数:4
相关论文
共 30 条
[11]   A common solution to group 2 influenza virus neutralization [J].
Friesen, Robert H. E. ;
Lee, Peter S. ;
Stoop, Esther J. M. ;
Hoffman, Ryan M. B. ;
Ekiert, Damian C. ;
Bhabha, Gira ;
Yu, Wenli ;
Juraszek, Jarek ;
Koudstaal, Wouter ;
Jongeneelen, Mandy ;
Korse, Hans J. W. M. ;
Ophorst, Carla ;
Brinkman-van der Linden, Els C. M. ;
Throsby, Mark ;
Kwakkenbos, Mark J. ;
Bakker, Arjen Q. ;
Beaumont, Tim ;
Spits, Hergen ;
Kwaks, Ted ;
Vogels, Ronald ;
Ward, Andrew B. ;
Goudsmit, Jaap ;
Wilson, Ian A. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 111 (01) :445-450
[12]   INTRODUCTION OF INTERSUBUNIT DISULFIDE BONDS IN THE MEMBRANE-DISTAL REGION OF THE INFLUENZA HEMAGGLUTININ ABOLISHES MEMBRANE-FUSION ACTIVITY [J].
GODLEY, L ;
PFEIFER, J ;
STEINHAUER, D ;
ELY, B ;
SHAW, G ;
KAUFMANN, R ;
SUCHANEK, E ;
PABO, C ;
SKEHEL, JJ ;
WILEY, DC ;
WHARTON, S .
CELL, 1992, 68 (04) :635-645
[13]   H5 avian and H9 swine influenza virus haemagglutinin structures: possible origin of influenza subtypes [J].
Ha, Y ;
Stevens, DJ ;
Skehel, JJ ;
Wiley, DC .
EMBO JOURNAL, 2002, 21 (05) :865-875
[14]   Antibody Recognition of the Pandemic H1N1 Influenza Virus Hemagglutinin Receptor Binding Site [J].
Hong, Minsun ;
Lee, Peter S. ;
Hoffman, Ryan M. B. ;
Zhu, Xueyong ;
Krause, Jens C. ;
Laursen, Nick S. ;
Yoon, Sung-il ;
Song, Langzhou ;
Tussey, Lynda ;
Crowe, James E., Jr. ;
Ward, Andrew B. ;
Wilson, Ian A. .
JOURNAL OF VIROLOGY, 2013, 87 (22) :12471-12480
[15]   Influenza virus hemagglutinin stalk-based antibodies and vaccines [J].
Krammer, Florian ;
Palese, Peter .
CURRENT OPINION IN VIROLOGY, 2013, 3 (05) :521-530
[16]   Reversible inhibition of the fusion activity of measles virus F protein by an engineered intersubunit disulfide bridge [J].
Lee, Jin K. ;
Prussia, Andrew ;
Snyder, James P. ;
Plemper, Richard K. .
JOURNAL OF VIROLOGY, 2007, 81 (16) :8821-8826
[17]   Structural Characterization of Viral Epitopes Recognized by Broadly Cross-Reactive Antibodies [J].
Lee, Peter S. ;
Wilson, Ian A. .
INFLUENZA PATHOGENESIS AND CONTROL - VOL II, 2015, 386 :323-341
[18]   Receptor mimicry by antibody F045-092 facilitates universal binding to the H3 subtype of influenza virus [J].
Lee, Peter S. ;
Ohshima, Nobuko ;
Stanfield, Robyn L. ;
Yu, Wenli ;
Iba, Yoshitaka ;
Okuno, Yoshinobu ;
Kurosawa, Yoshikazu ;
Wilson, Ian A. .
NATURE COMMUNICATIONS, 2014, 5
[19]   Production and stabilization of the trimeric influenza hemagglutinin stem domain for potentially broadly protective influenza vaccines [J].
Lu, Yuan ;
Welsh, John P. ;
Swartz, James R. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 111 (01) :125-130
[20]   Influenza hemagglutinin stem-fragment immunogen elicits broadly neutralizing antibodies and confers heterologous protection [J].
Mallajosyula, Vamsee V. A. ;
Citron, Michael ;
Ferrara, Francesca ;
Lu, Xianghan ;
Callahan, Cheryl ;
Heidecker, Gwendolyn J. ;
Sarma, Siddhartha P. ;
Flynn, Jessica A. ;
Temperton, Nigel J. ;
Liang, Xiaoping ;
Varadarajan, Raghavan .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 111 (25) :E2514-E2523