A highly potent human antibody neutralizes dengue virus serotype 3 by binding across three surface proteins

被引：164

作者：

Fibriansah, Guntur ^{[1
,2
]}

Tan, Joanne L. ^{[1
,2
]}

Smith, Scott A. ^{[3
,4
]}

de Alwis, Ruklanthi ^{[5
]}

Ng, Thiam-Seng ^{[1
,2
]}

Kostyuchenko, Victor A. ^{[1
,2
]}

Jadi, Ramesh S. ^{[5
]}

Kukkaro, Petra ^{[1
,2
]}

de Silva, Aravinda M. ^{[5
]}

Crowe, James E. ^{[4
,6
,7
]}

Lok, Shee-Mei ^{[1
,2
]}

机构：

[1] Duke NUS Grad Med Sch, Program Emerging Infect Dis, Singapore 169857, Singapore

[2] Natl Univ Singapore, Ctr BioImaging Sci, Singapore 117557, Singapore

[3] Vanderbilt Univ, Dept Med, Nashville, TN 37232 USA

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

[5] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA

[6] Vanderbilt Univ, Med Ctr, Dept Pediat, Microbiol & Immunol, Nashville, TN 37232 USA

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

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

关键词：

HUMAN MONOCLONAL-ANTIBODIES; MEMORY B-CELLS; ENVELOPE GLYCOPROTEIN; DOMAIN-III; MOLECULAR-DYNAMICS; ELECTRON-MICROSCOPY; MEMBRANE-FUSION; INFECTION; EPITOPES; TYPE-2;

D O I：

10.1038/ncomms7341

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：

Dengue virus (DENV) infects similar to 400 million people annually. There is no licensed vaccine or therapeutic drug. Only a small fraction of the total DENV-specific antibodies in a naturally occurring dengue infection consists of highly neutralizing antibodies. Here we show that the DENV-specific human monoclonal antibody 5J7 is exceptionally potent, neutralizing 50% of virus at nanogram-range antibody concentration. The 9 A resolution cryo-electron microscopy structure of the Fab 5J7-DENV complex shows that a single Fab molecule binds across three envelope proteins and engages three functionally important domains, each from a different envelope protein. These domains are critical for receptor binding and fusion to the endosomal membrane. The ability to bind to multiple domains allows the antibody to fully coat the virus surface with only 60 copies of Fab, that is, half the amount compared with other potent antibodies. Our study reveals a highly efficient and unusual mechanism of molecular recognition by an antibody.

引用

页数：10

共 58 条

[1] The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling [J].

Arnold, K ;

Bordoli, L ;

Kopp, J ;

Schwede, T .

BIOINFORMATICS, 2006, 22 (02) :195-201

[2] The Human Immune Response to Dengue Virus Is Dominated by Highly Cross-Reactive Antibodies Endowed with Neutralizing and Enhancing Activity [J].

Beltramello, Martina ;

Williams, Katherine L. ;

Simmons, Cameron P. ;

Macagno, Annalisa ;

Simonelli, Luca ;

Quyen, Nguyen Than Ha ;

Sukupolvi-Petty, Soila ;

Navarro-Sanchez, Erika ;

Young, Paul R. ;

de Silva, Aravinda M. ;

Rey, Felix A. ;

Varani, Luca ;

Whitehead, Stephen S. ;

Diamond, Michael S. ;

Harris, Eva ;

Lanzavecchia, Antonio ;

Sallusto, Federica .

CELL HOST & MICROBE, 2010, 8 (03) :271-283

[3] The global distribution and burden of dengue [J].

Bhatt, Samir ;

Gething, Peter W. ;

Brady, Oliver J. ;

Messina, Jane P. ;

Farlow, Andrew W. ;

Moyes, Catherine L. ;

Drake, John M. ;

Brownstein, John S. ;

Hoen, Anne G. ;

Sankoh, Osman ;

Myers, Monica F. ;

George, Dylan B. ;

Jaenisch, Thomas ;

Wint, G. R. William ;

Simmons, Cameron P. ;

Scott, Thomas W. ;

Farrar, Jeremy J. ;

Hay, Simon I. .

NATURE, 2013, 496 (7446) :504-507

[4] Structure of a flavivirus envelope glycoprotein in its low-pH-induced membrane fusion conformation [J].

Bressanelli, S ;

Stiasny, K ;

Allison, SL ;

Stura, EA ;

Duquerroy, S ;

Lescar, J ;

Heinz, FX ;

Rey, FA .

EMBO JOURNAL, 2004, 23 (04) :728-738

[5] The envelope glycoprotein domain III of dengue virus serotypes 1 and 2 inhibit virus entry [J].

Chin, J. F. L. ;

Chu, J. J. H. ;

Ng, M. L. .

MICROBES AND INFECTION, 2007, 9 (01) :1-6

[6] MULTIPLE SEQUENCE ALIGNMENT WITH HIERARCHICAL-CLUSTERING [J].

CORPET, F .

NUCLEIC ACIDS RESEARCH, 1988, 16 (22) :10881-10890

[7] Mechanistic Study of Broadly Neutralizing Human Monoclonal Antibodies against Dengue Virus That Target the Fusion Loop [J].

Costin, Joshua M. ;

Zaitseva, Elena ;

Kahle, Kristen M. ;

Nicholson, Cindo O. ;

Rowe, Dawne K. ;

Graham, Amanda S. ;

Bazzone, Lindsey E. ;

Hogancamp, Greg ;

Sierra, Marielys Figueroa ;

Fong, Rachel H. ;

Yang, Sung-Tae ;

Lin, Li ;

Robinson, James E. ;

Doranz, Benjamin J. ;

Chernomordik, Leonid V. ;

Michael, Scott F. ;

Schieffelin, John S. ;

Isern, Sharon .

JOURNAL OF VIROLOGY, 2013, 87 (01) :52-66

[8] Identification of human neutralizing antibodies that bind to complex epitopes on dengue virions [J].

de Alwis, Ruklanthi ;

Smith, Scott A. ;

Olivarez, Nicholas P. ;

Messer, William B. ;

Huynh, Jeremy P. ;

Wahala, Wahala M. P. B. ;

White, Laura J. ;

Diamond, Michael S. ;

Baric, Ralph S. ;

Crowe, James E., Jr. ;

de Silva, Aravinda M. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (19) :7439-7444

[9] Features and development of Coot [J].

Emsley, P. ;

Lohkamp, B. ;

Scott, W. G. ;

Cowtan, K. .

ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 2010, 66 :486-501

[10] A potent anti-dengue human antibody preferentially recognizes the conformation of E protein monomers assembled on the virus surface [J].

Fibriansah, Guntur ;

Tan, Joanne L. ;

Smith, Scott A. ;

de Alwis, Adamberage R. ;

Thiam-Seng Ng ;

Kostyuchenko, Victor A. ;

Ibarra, Kristie D. ;

Wang, Jiaqi ;

Harris, Eva ;

de Silva, Aravinda ;

Crowe, James E., Jr. ;

Lok, Shee-Mei .

EMBO MOLECULAR MEDICINE, 2014, 6 (03) :358-371

← 1 2 3 4 5 6 →