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DOI | 10.1038/ncomms14326 |
Cross-reactive neutralizing human survivor monoclonal antibody BDBV223 targets the ebolavirus stalk | |
King, Liam B.1; West, Brandyn R.1; Moyer, Crystal L.1; Gilchuk, Pavlo2; Flyak, Andrew3,4,5; Ilinykh, Philipp A.6,7; Bombardi, Robin2; Hui, Sean1; Huang, Kai6,7; Bukreyev, Alexander6,7,8; Crowe, James E., Jr.2,3,4,5; Saphire, Erica Ollmann1,9,10 | |
2019-04-17 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2019 |
卷号 | 10 |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | Three Ebolavirus genus viruses cause lethal disease and lack targeted therapeutics: Ebola virus, Sudan virus and Bundibugyo virus. Monoclonal antibody (mAb) cocktails against the surface glycoprotein (GP) present a potential therapeutic strategy. Here we report two crystal structures of the antibody BDBV223, alone and complexed with its GP2 stalk epitope, an interesting site for therapeutic/vaccine design due to its high sequence conservation among ebolaviruses. BDBV223, identified in a human survivor of Bundibugyo virus disease, neutralizes both Bundibugyo virus and Ebola virus, but not Sudan virus. Importantly, the structure suggests that BDBV223 binding interferes with both the trimeric bundle assembly of GP and the viral membrane by stabilizing a conformation in which the monomers are separated by GP lifting or bending. Targeted mutagenesis of BDBV223 to enhance SUDV GP recognition indicates that additional determinants of antibody binding likely lie outside the visualized interactions, and perhaps involve quaternary assembly or membrane-interacting regions. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000464976200001 |
WOS关键词 | VIRUS GLYCOPROTEIN ; ENVELOPE ; ENTRY ; GP2 |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/203223 |
专题 | 资源环境科学 |
作者单位 | 1.Scripps Res Inst, Dept Immunol & Microbiol, La Jolla, CA 92037 USA; 2.Vanderbilt Univ, Med Ctr, Vanderbilt Vaccine Ctr, Nashville, TN 37232 USA; 3.Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA; 4.Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA; 5.Vanderbilt Univ, Med Ctr, Dept Microbiol & Immunol, Nashville, TN 37232 USA; 6.Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA; 7.Galveston Natl Lab, Galveston, TX 77555 USA; 8.Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA; 9.Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA; 10.La Jolla Inst Immunol, La Jolla, CA 92037 USA |
推荐引用方式 GB/T 7714 | King, Liam B.,West, Brandyn R.,Moyer, Crystal L.,et al. Cross-reactive neutralizing human survivor monoclonal antibody BDBV223 targets the ebolavirus stalk[J]. NATURE COMMUNICATIONS,2019,10. |
APA | King, Liam B..,West, Brandyn R..,Moyer, Crystal L..,Gilchuk, Pavlo.,Flyak, Andrew.,...&Saphire, Erica Ollmann.(2019).Cross-reactive neutralizing human survivor monoclonal antibody BDBV223 targets the ebolavirus stalk.NATURE COMMUNICATIONS,10. |
MLA | King, Liam B.,et al."Cross-reactive neutralizing human survivor monoclonal antibody BDBV223 targets the ebolavirus stalk".NATURE COMMUNICATIONS 10(2019). |
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