Structures of the Zika Virus Envelope Protein and Its Complex with a Flavivirus Broadly Protective Antibody

被引:395
作者
Dai, Lianpan [1 ]
Song, Jian [2 ,3 ]
Lu, Xishan [4 ]
Deng, Yong-Qiang [5 ]
Musyoki, Abednego Moki [2 ,3 ]
Cheng, Huijun [1 ]
Zhang, Yanfang [4 ]
Yuan, Yuan [2 ,3 ]
Song, Hao [2 ,3 ]
Haywood, Joel [2 ,3 ]
Xiao, Haixia [4 ]
Yan, Jinghua [2 ,3 ,6 ,7 ,8 ]
Shi, Yi [1 ,2 ,3 ,6 ,7 ]
Qin, Cheng-Feng [5 ]
Qi, Jianxun [2 ]
Gao, George F. [1 ,2 ,3 ,4 ,6 ,7 ,9 ,10 ]
机构
[1] Chinese Acad Sci, Beijing Inst Life Sci, Res Network Immun & Hlth RNIH, Beijing 100101, Peoples R China
[2] Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing 100071, Peoples R China
[3] Univ Chinese Acad Sci, Savaid Med Sch, Beijing 100049, Peoples R China
[4] Chinese Acad Sci, Tianjin Inst Ind Biotechnol, Tianjin 300308, Peoples R China
[5] Beijing Inst Microbiol & Epidemiol, State Key Lab Pathogen & Biosecur, Beijing 100101, Peoples R China
[6] Shenzhen Third Peoples Hosp, Shenzhen Key Lab Pathogen & Immun, Shenzhen 518112, Peoples R China
[7] Chinese Acad Sci, Ctr Influenza Res & Early Warning CASCIRE, Beijing 100101, Peoples R China
[8] Chinese Acad Sci, Inst Microbiol, CAS Key Lab Microbial Physiol & Engn, Beijing 100101, Peoples R China
[9] Collaborat Innovat Ctr Diag & Treatment Infect Di, Hangzhou 310003, Zhejiang, Peoples R China
[10] Chinese Ctr Dis Control & Prevent China CDC, Natl Inst Viral Dis Control & Prevent, Beijing 102206, Peoples R China
基金
中国国家自然科学基金;
关键词
WEST-NILE-VIRUS; CROSS-REACTIVE ANTIBODIES; HUMAN MONOCLONAL-ANTIBODIES; DENGUE VIRUS; FUSION-LOOP; NEUTRALIZING ANTIBODIES; EBOLA-VIRUS; ENCEPHALITIS-VIRUS; CRYSTAL-STRUCTURE; ASIAN LINEAGE;
D O I
10.1016/j.chom.2016.04.013
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Zika virus (ZIKV), a mosquito-borne flavivirus, is a current global public health concern. The flavivirus envelope (E) glycoprotein is responsible for virus entry and represents a major target of neutralizing antibodies for other flaviviruses. Here, we report the structures of ZIKV E protein at 2.0 angstrom and in complex with a flavivirus broadly neutralizing murine antibody 2A10G6 at 3.0 angstrom. ZIKV-E resembles all the known flavivirus E structures but contains a unique, positively charged patch adjacent to the fusion loop region of the juxtaposed monomer, which may influence host attachment. The ZIKV-E-2A10G6 complex structure reveals antibody recognition of a highly conserved fusion loop. 2A10G6 binds to ZIKV-E with high affinity in vitro and neutralizes currently circulating ZIKV strains in vitro and in mice. The E protein fusion loop epitope represents a potential candidate for therapeutic antibodies against ZIKV.
引用
收藏
页码:696 / 704
页数:9
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