PropertyValue
?:abstract
  • E1 and E2 (E1E2), the entry proteins of Hepatitis C Virus (HCV), are unlike that of any other virus yet described, and the detailed molecular mechanisms of HCV entry/fusion remain unknown. Hypervariable region-1 (HVR-1) of E2 is a putative intrinsically disordered protein tail. Here, we demonstrate that HVR-1 has an autoinhibitory function that suppresses the activity of E1E2 on free virions; this is dependent on its conformational entropy. Crucially, to allow entry, this mechanism is turned off by host receptor interactions at the cell surface. Thus, HVR-1 is akin to a safety catch on E1E2 activity. Mutations that reduce conformational entropy in HVR-1, or genetic deletion of HVR-1, turn off the safety catch to generate hyper-reactive HCV that exhibits enhanced virus entry but is thermally unstable and acutely sensitive to neutralising antibodies. Therefore, the HVR-1 safety catch controls the efficiency of virus entry and maintains resistance to neutralising antibodies.
is ?:annotates of
?:creator
?:doi
  • 10.1101/2020.11.11.377218
?:doi
?:externalLink
?:journal
  • bioRxiv
?:license
  • biorxiv
?:pdf_json_files
  • document_parses/pdf_json/37344bd8fcbd5ba1bdb6cbebc012e228e3ab425a.json
?:publication_isRelatedTo_Disease
?:sha_id
?:source
  • BioRxiv
?:title
  • An Entropic Safety Catch Controls Hepatitis C Virus Entry and Antibody Resistance
?:type
?:year
  • 2020-11-16

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