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c-Src is required for complex formation between the hepatitis C virus-encoded proteins NS5A and NS5B: a prerequisite for replication

Hepatitis C virus (HCV) is a leading cause of chronic liver disease worldwide and establishes a persistent infection in more than 60% of infected individuals. This high frequency of persistent infection indicates that HCV has evolved efficient strategies to interfere with the adaptive and innate imm...

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Hauptverfasser: Pfannkuche, Andreas (VerfasserIn) , Büther, Katrin (VerfasserIn) , Karthe, Juliane (VerfasserIn) , Pönisch, Marion (VerfasserIn) , Bartenschlager, Ralf (VerfasserIn) , Trilling, Mirko (VerfasserIn) , Hengel, Hartmut (VerfasserIn) , Willbold, Dieter (VerfasserIn) , Häussinger, Dieter (VerfasserIn) , Bode, Johannes Georg (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 31 January 2011
In: Hepatology
Year: 2011, Jahrgang: 53, Heft: 4, Pages: 1127-1136
ISSN:1527-3350
DOI:10.1002/hep.24214
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1002/hep.24214
Volltext
Verfasserangaben:Andreas Pfannkuche, Katrin Büther, Juliane Karthe, Marion Poenisch, Ralf Bartenschlager, Mirko Trilling, Hartmut Hengel, Dieter Willbold, Dieter Häussinger, and Johannes Georg Bode
Beschreibung
Zusammenfassung:Hepatitis C virus (HCV) is a leading cause of chronic liver disease worldwide and establishes a persistent infection in more than 60% of infected individuals. This high frequency of persistent infection indicates that HCV has evolved efficient strategies to interfere with the adaptive and innate immune response and to occupy and use host cell infrastructure. The present study provides evidence that c-Src, a member of the Src family kinases that participates in many signal transduction pathways, represents an essential host factor exploited for viral replication. c-Src directly interacts with the viral RNA-dependent RNA polymerase (NS5B) via its SH3 domain and with the nonstructural phosphoprotein NS5A via its SH2 domain. Both interactions are required to maintain the protein-protein interaction of NS5A and NS5B, which has been previously demonstrated to be essential for viral replication. Accordingly, HCV genome replication and production of the viral proteins was strongly reduced upon small interfering RNA-mediated knockdown of c-Src or in the presence of the tyrosine kinase inhibitor herbimycin A. This effect could not be rescued by supplementation of the two other ubiquitously expressed Src family kinases Fyn or Yes. - CONCLUSION: Our data suggest that c-Src participates in the formation of an NS5A/NS5B protein complex that is required for efficient replication of HCV.
Beschreibung:Gesehen am 05.12.2022
Beschreibung:Online Resource
ISSN:1527-3350
DOI:10.1002/hep.24214

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