Cryo-EM structure of an antibody that neutralizes dengue virus type 2 by locking E protein dimers

被引：184

作者：

Fibriansah, Guntur ^{[1
,2
]}

Ibarra, Kristie D. ^{[3
]}

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

Smith, Scott A. ^{[4
,5
]}

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

Lim, Xin-Ni ^{[1
,2
]}

Ooi, Justin S. G. ^{[1
,2
]}

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

Wang, Jiaqi ^{[1
,2
]}

de Silva, Aravinda M. ^{[6
]}

Harris, Eva ^{[3
]}

Crowe, James E., Jr. ^{[5
,7
,8
]}

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

机构：

[1] Duke Natl Univ Singapore Grad Med Sch, Program Emerging Infect Dis, Singapore, Singapore

[2] Natl Univ Singapore, Ctr BioImaging Sci, Singapore 117548, Singapore

[3] Univ Calif Berkeley, Sch Publ Hlth, Div Infect Dis & Vaccinol, Berkeley, CA 94720 USA

[4] Vanderbilt Univ, Dept Med, Nashville, TN USA

[5] Vanderbilt Univ, Vanderbilt Vaccine Ctr, Nashville, TN 37235 USA

[6] Univ N Carolina, Sch Med, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA

[7] Vanderbilt Univ, Dept Pediat, Nashville, TN USA

[8] Vanderbilt Univ, Dept Pathol Microbiol & Immunol, Nashville, TN USA

来源：

SCIENCE | 2015年 / 349卷 / 6243期

关键词：

VACCINE;

D O I：

10.1126/science.aaa8651

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：

There are four closely-related dengue virus (DENV) serotypes. Infection with one serotype generates antibodies that may cross-react and enhance infection with other serotypes in a secondary infection. We demonstrated that DENV serotype 2 (DENV2)-specific human monoclonal antibody (HMAb) 2D22 is therapeutic in a mouse model of antibody-enhanced severe dengue disease. We determined the cryo-electron microscopy (cryo-EM) structures of HMAb 2D22 complexed with two different DENV2 strains. HMAb 2D22 binds across viral envelope (E) proteins in the dimeric structure, which probably blocks the E protein reorganization required for virus fusion. HMAb 2D22 "locks" two-thirds of or all dimers on the virus surface, depending on the strain, but neutralizes these DENV2 strains with equal potency. The epitope defined by HMAb 2D22 is a potential target for vaccines and therapeutics.

引用

页码：88 / 91

页数：4

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