TY  - JOUR
AU  - Hellert, Jan
AU  - Aebischer, Andrea
AU  - Haouz, Ahmed
AU  - Guardado-Calvo, Pablo
AU  - Reiche, Sven
AU  - Beer, Martin
AU  - Rey, Félix A.
TI  - Structure, function, and evolution of the Orthobunyavirus membrane fusion glycoprotein
JO  - Cell reports
VL  - 42
IS  - 3
SN  - 2211-1247
CY  - [New York, NY]
PB  - Elsevier
M1  - PUBDB-2024-05665
SP  - 112142 
PY  - 2023
AB  - 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 (GcS) targeted by the patients’ antibody response and a conserved C-terminal moiety (GcF) responsible for membrane fusion during cell entry. Here, we report the X-ray structure of post-fusion La Crosse and Schmallenberg virus GcF, 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 GcS-GcF junction. The resulting knowledge provides essential molecular underpinnings for future development of potential therapeutic treatments and vaccines. 
LB  - PUB:(DE-HGF)16
C6  - pmid:36827185
UR  - <Go to ISI:>//WOS:000944867800001
DO  - DOI:10.1016/j.celrep.2023.112142
UR  - https://bib-pubdb1.desy.de/record/613886
ER  -