Structure, function, and evolution of the Orthobunyavirus membrane fusion glycoprotein.
Cell Rep
; 42(3): 112142, 2023 03 28.
Article
em En
| MEDLINE
| ID: mdl-36827185
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 (â¼1,000 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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Orthobunyavirus
/
Vírus La Crosse
Limite:
Child
/
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article