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.
Highlights
To cite this version: Akaash Mishra, Jan Hellert, Natalia Freitas, Pablo Guardado-Calvo, Ahmed Haouz, et al
The documents may come from teaching and research institutions in France or abroad, or from public or private research centers
Structural information is lacking in regard to the Crimean-Congo hemorrhagic fever virus (CCHFV) membrane fusion glycoprotein Gc—the main target of the host neutralizing antibody response—as well as antibody–mediated neutralization mechanisms
Summary
To cite this version: Akaash Mishra, Jan Hellert, Natalia Freitas, Pablo Guardado-Calvo, Ahmed Haouz, et al. In CCHFV, the HMIS conformation is further supported by a hydrogen bond network that involves the buried polar side chains of Asn1194 and Arg1189 of the cd loop in both the pre- and postfusion forms (Fig. 2, A to C).
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.