Buchumschlag

Hepatitis C virus NS3 helicase contributes to (−) strand RNA synthesis

Many positive strand RNA viruses encode helicases, but their distinct functions in viral replication cycles is poorly understood. Here, we identify a mutation in the helicase domain of HCV non-structural protein 3 (NS3h), D1467G, which specifically affects (−) strand synthesis, phenocopying mutation...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Hauptverfasser: Ralfs, Philipp (VerfasserIn) , Bressanelli, Stéphane (VerfasserIn) , Günter, Lina M. (VerfasserIn) , Gabel, Alexander (VerfasserIn) , Rothhaar, Paul (VerfasserIn) , Price, Kyle J. (VerfasserIn) , Tubiana, Thibault (VerfasserIn) , Munschauer, Mathias (VerfasserIn) , Frick, David N. (VerfasserIn) , Lohmann, Volker (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 27 August 2025
In: Nature Communications
Year: 2025, Jahrgang: 16, Pages: 1-21
ISSN:2041-1723
DOI:10.1038/s41467-025-63498-9
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41467-025-63498-9
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41467-025-63498-9
Volltext
Verfasserangaben:Philipp Ralfs, Stéphane Bressanelli, Lina M. Günter, Alexander Gabel, Paul Rothhaar, Kyle J. Price, Thibault Tubiana, Mathias Munschauer, David N. Frick, and Volker Lohmann
Beschreibung
Zusammenfassung:Many positive strand RNA viruses encode helicases, but their distinct functions in viral replication cycles is poorly understood. Here, we identify a mutation in the helicase domain of HCV non-structural protein 3 (NS3h), D1467G, which specifically affects (−) strand synthesis, phenocopying mutations in the 3’ untranslated region of the genome. D1467G does not impair helicase activity in vitro or the binding of NS3h to critical cis-acting RNA elements, but reduces the interaction of NS3h and NS5B polymerase, potentially contributing to defective (−) strand synthesis. AlphaFold predictions of complexes between NS3h, RNA and/or NS5B suggest that NS3h both remodels the cis-acting RNA elements and unwinds the terminal stem-loop of the HCV genome rendering the template accessible for de novo initiation of (−) strand synthesis by NS5B. Overall, our study provides evidence for a defined function of a viral helicase in (−) strand genome synthesis of a positive strand RNA virus.
Beschreibung:Gesehen am 03.02.2026
Beschreibung:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-025-63498-9

Ähnliche Einträge