Mechanism of Human Antibody-Mediated Neutralization of Marburg Virus

被引：134

作者：

Flyak, Andrew I. ^{[1
]}

Ilinykh, Philipp A. ^{[5
,6
]}

Murin, Charles D. ^{[7
,8
]}

Garron, Tania ^{[5
,6
]}

Shen, Xiaoli ^{[5
,6
]}

Fusco, Marnie L. ^{[8
]}

Hashiguchi, Takao ^{[8
]}

Bornholdt, Zachary A. ^{[8
]}

Slaughter, James C. ^{[3
,4
]}

Sapparapu, Gopal ^{[3
]}

Klages, Curtis ^{[5
,6
]}

Ksiazek, Thomas G. ^{[5
,6
]}

Ward, Andrew B. ^{[7
]}

Saphire, Erica Ollmann ^{[8
,9
]}

Bukreyev, Alexander ^{[5
,6
]}

Crowe, James E., Jr. ^{[1
,2
,3
]}

机构：

[1] Vanderbilt Univ, Dept Pathol Microbiol & Immunol, Nashville, TN 37232 USA

[2] Vanderbilt Univ, Dept Pediat, Nashville, TN 37232 USA

[3] Vanderbilt Univ, Vanderbilt Vaccine Ctr, Nashville, TN 37232 USA

[4] Vanderbilt Univ, Dept Biostat, Nashville, TN 37232 USA

[5] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA

[6] Galveston Natl Lab, Galveston, TX 77550 USA

[7] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA

[8] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA

[9] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA

来源：

CELL | 2015年 / 160卷 / 05期

关键词：

VESICULAR STOMATITIS-VIRUS; EBOLA-VIRUS; NONHUMAN-PRIMATES; SYSTEM; GLYCOPROTEIN; LEGINON; ACQUISITION; GENERATION; MICROSCOPY; PROTECTION;

D O I：

10.1016/j.cell.2015.01.031

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The mechanisms by which neutralizing antibodies inhibit Marburg virus (MARV) are not known. We isolated a panel of neutralizing antibodies from a human MARV survivor that bind to MARV glycoprotein (GP) and compete for binding to a single major antigenic site. Remarkably, several of the antibodies also bind to Ebola virus (EBOV) GP. Single-particle EM structures of antibody-GP complexes reveal that all of the neutralizing antibodies bind to MARV GP at or near the predicted region of the receptor-binding site. The presence of the glycan cap or mucin-like domain blocks binding of neutralizing antibodies to EBOV GP, but not to MARV GP. The data suggest that MARV-neutralizing antibodies inhibit virus by binding to infectious virions at the exposed MARV receptor-binding site, revealing a mechanism of filovirus inhibition.

引用

页码：893 / 903

页数：11

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