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000015093 0247_ $$2pmid$$apmid:21480319
000015093 0247_ $$2DOI$$a10.1002/hep.24214
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000015093 041__ $$aeng
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000015093 084__ $$2WoS$$aGastroenterology & Hepatology
000015093 1001_ $$0P:(DE-Juel1)VDB98446$$aPfannkuche, A.$$b0$$uFZJ
000015093 245__ $$aC-Src is required for complex formation between the hepatitis C virus–encoded proteins NS5A and NS5B: A prerequisite for replication
000015093 260__ $$aNew York [u.a.]$$bWiley Interscience$$c2011
000015093 300__ $$a1127 - 1136
000015093 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article
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000015093 3367_ $$2BibTeX$$aARTICLE
000015093 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000015093 3367_ $$2DRIVER$$aarticle
000015093 440_0 $$011862$$aHepatology$$v53$$x0270-9139$$y4
000015093 500__ $$aSupported by the German Research Foundation through the following grants: FOR 729 (Teilprojekt 7 to J. B. and D. H.), SFB 575, and GK 1045 and SFB 638 (Teilprojekt 5 to R. B.). M. P. is supported by the Postdoc Fellowship of the Medical Faculty of Heidelberg. J. B. is supported by the Heisenberg Program of the German Research Foundation.
000015093 520__ $$aHepatitis 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.
000015093 536__ $$0G:(DE-Juel1)FUEK409$$2G:(DE-HGF)$$aFunktion und Dysfunktion des Nervensystems$$cP33$$x0
000015093 536__ $$0G:(DE-Juel1)FUEK505$$2G:(DE-HGF)$$aBioSoft: Makromolekulare Systeme und biologische Informationsverarbeitung$$cP45$$x1
000015093 588__ $$aDataset connected to Web of Science, Pubmed
000015093 650_2 $$2MeSH$$aBenzoquinones: pharmacology
000015093 650_2 $$2MeSH$$aCell Line, Tumor
000015093 650_2 $$2MeSH$$aHepacivirus: genetics
000015093 650_2 $$2MeSH$$aHepacivirus: physiology
000015093 650_2 $$2MeSH$$aHumans
000015093 650_2 $$2MeSH$$aLactams, Macrocyclic: pharmacology
000015093 650_2 $$2MeSH$$aRNA Replicase: genetics
000015093 650_2 $$2MeSH$$aViral Nonstructural Proteins
000015093 650_2 $$2MeSH$$aVirus Replication
000015093 650_2 $$2MeSH$$asrc Homology Domains: genetics
000015093 650_2 $$2MeSH$$asrc-Family Kinases: physiology
000015093 650_7 $$00$$2NLM Chemicals$$aBenzoquinones
000015093 650_7 $$00$$2NLM Chemicals$$aLactams, Macrocyclic
000015093 650_7 $$00$$2NLM Chemicals$$aNS-5 protein, hepatitis C virus
000015093 650_7 $$00$$2NLM Chemicals$$aViral Nonstructural Proteins
000015093 650_7 $$070563-58-5$$2NLM Chemicals$$aherbimycin
000015093 650_7 $$0EC 2.7.10.2$$2NLM Chemicals$$asrc-Family Kinases
000015093 650_7 $$0EC 2.7.7.48$$2NLM Chemicals$$aRNA Replicase
000015093 650_7 $$2WoSType$$aJ
000015093 7001_ $$0P:(DE-Juel1)VDB98447$$aBüther, K.$$b1$$uFZJ
000015093 7001_ $$0P:(DE-Juel1)VDB98448$$aKarthe, J.$$b2$$uFZJ
000015093 7001_ $$0P:(DE-Juel1)VDB98449$$aPoenisch, M.$$b3$$uFZJ
000015093 7001_ $$0P:(DE-Juel1)VDB98450$$aBartenschlager, R.$$b4$$uFZJ
000015093 7001_ $$0P:(DE-Juel1)VDB98451$$aTrilling, M.$$b5$$uFZJ
000015093 7001_ $$0P:(DE-Juel1)VDB98452$$aHengel, H.$$b6$$uFZJ
000015093 7001_ $$0P:(DE-Juel1)132029$$aWillbold, D.$$b7$$uFZJ
000015093 7001_ $$0P:(DE-Juel1)VDB9577$$aHäussinger, D.$$b8$$uFZJ
000015093 7001_ $$0P:(DE-Juel1)VDB98456$$aBode, J. G.$$b9$$uFZJ
000015093 773__ $$0PERI:(DE-600)1472120-x$$a10.1002/hep.24214$$gVol. 53, p. 1127 - 1136$$p1127 - 1136$$q53<1127 - 1136$$tHepatology$$v53$$x0270-9139$$y2011
000015093 8567_ $$uhttp://dx.doi.org/10.1002/hep.24214
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000015093 9141_ $$y2011
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000015093 9132_ $$0G:(DE-HGF)POF3-553$$1G:(DE-HGF)POF3-550$$2G:(DE-HGF)POF3-500$$aDE-HGF$$bKey Technologies$$lBioSoft  Fundamentals for future Technologies in the fields of Soft Matter and Life Sciences$$vPhysical Basis of Diseases$$x0
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