Structure, function, and evolution of the Orthobunyavirus membrane fusion glycoprotein.
Hellert, J., Aebischer, A., Haouz, A., Guardado-Calvo, P., Reiche, S., Beer, M., Rey, F.A.(2023) Cell Rep 42: 112142-112142
- PubMed: 36827185
- DOI: https://doi.org/10.1016/j.celrep.2023.112142
- Primary Citation of Related Structures:
7A56, 7A57 - PubMed Abstract:
La Crosse virus, responsible for pediatric encephalitis in the United States, and Schmallenberg virus, a highly teratogenic veterinary virus in Europe, belong to the large Orthobunyavirus genus of zoonotic arthropod-borne pathogens distributed worldwide. Viruses in this under-studied genus cause CNS infections or fever with debilitating arthralgia/myalgia syndromes, with no effective treatment. The main surface antigen, glycoprotein Gc (∼1,000 residues), has a variable N-terminal half (Gc S ) targeted by the patients' antibody response and a conserved C-terminal moiety (Gc F ) responsible for membrane fusion during cell entry. Here, we report the X-ray structure of post-fusion La Crosse and Schmallenberg virus Gc F , revealing the molecular determinants for hairpin formation and trimerization required to drive membrane fusion. We further experimentally confirm the role of residues in the fusion loops and in a vestigial endoplasmic reticulum (ER) translocation sequence at the Gc S -Gc F junction. The resulting knowledge provides essential molecular underpinnings for future development of potential therapeutic treatments and vaccines.
Organizational Affiliation:
Structural Virology Unit, Institut Pasteur - Université Paris-Cité, CNRS UMR 3569, 25-28 rue du Dr. Roux, 75015 Paris, France; Centre for Structural Systems Biology (CSSB), Leibniz-Institut für Virologie (LIV), Notkestraße 85, 22607 Hamburg, Germany.