Structural basis of synergistic neutralization of Crimean-Congo hemorrhagic fever virus by human antibodies.
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| Title: | Structural basis of synergistic neutralization of Crimean-Congo hemorrhagic fever virus by human antibodies. |
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| Authors: | Mishra, Akaash K., Hellert, Jan, Freitas, Natalia, Guardado-Calvo, Pablo, Haouz, Ahmed, Fels, J. Maximilian, Maurer, Daniel P., Abelson, Dafna M., Bornholdt, Zachary A., Walker, Laura M., Chandran, Kartik, Cosset, François-Loïc, McLellan, Jason S., Rey, Felix A. |
| Source: | Science (pre-March 2025). 1/7/2022, Vol. 375 Issue 6576, p104-109. 6p. 4 Color Photographs. |
| Subjects: | Hemorrhagic diseases, Human beings, Immunoglobulins, Zoonoses, Antigens |
| Abstract: | Crimean-Congo hemorrhagic fever virus (CCHFV) is the most widespread tick-borne zoonotic virus, with a 30% case fatality rate in humans. Structural information is lacking in regard to the CCHFV membrane fusion glycoprotein Gc—the main target of the host neutralizing antibody response—as well as antibody–mediated neutralization mechanisms. We describe the structure of prefusion Gc bound to the antigen-binding fragments (Fabs) of two neutralizing antibodies that display synergy when combined, as well as the structure of trimeric, postfusion Gc. The structures show the two Fabs acting in concert to block membrane fusion, with one targeting the fusion loops and the other blocking Gc trimer formation. The structures also revealed the neutralization mechanism of previously reported antibodies against CCHFV, providing the molecular underpinnings essential for developing CCHFV– specific medical countermeasures for epidemic preparedness. [ABSTRACT FROM AUTHOR] |
| Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Psychology and Behavioral Sciences Collection |
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| Abstract: | Crimean-Congo hemorrhagic fever virus (CCHFV) is the most widespread tick-borne zoonotic virus, with a 30% case fatality rate in humans. Structural information is lacking in regard to the CCHFV membrane fusion glycoprotein Gc—the main target of the host neutralizing antibody response—as well as antibody–mediated neutralization mechanisms. We describe the structure of prefusion Gc bound to the antigen-binding fragments (Fabs) of two neutralizing antibodies that display synergy when combined, as well as the structure of trimeric, postfusion Gc. The structures show the two Fabs acting in concert to block membrane fusion, with one targeting the fusion loops and the other blocking Gc trimer formation. The structures also revealed the neutralization mechanism of previously reported antibodies against CCHFV, providing the molecular underpinnings essential for developing CCHFV– specific medical countermeasures for epidemic preparedness. [ABSTRACT FROM AUTHOR] |
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| ISSN: | 00368075 |
| DOI: | 10.1126/science.abl6502 |
