001     15093
005     20200402210018.0
024 7 _ |2 pmid
|a pmid:21480319
024 7 _ |2 DOI
|a 10.1002/hep.24214
024 7 _ |2 WOS
|a WOS:000289419600008
037 _ _ |a PreJuSER-15093
041 _ _ |a eng
082 _ _ |a 610
084 _ _ |2 WoS
|a Gastroenterology & Hepatology
100 1 _ |0 P:(DE-Juel1)VDB98446
|a Pfannkuche, A.
|b 0
|u FZJ
245 _ _ |a C-Src is required for complex formation between the hepatitis C virus–encoded proteins NS5A and NS5B: A prerequisite for replication
260 _ _ |a New York [u.a.]
|b Wiley Interscience
|c 2011
300 _ _ |a 1127 - 1136
336 7 _ |a Journal Article
|0 PUB:(DE-HGF)16
|2 PUB:(DE-HGF)
336 7 _ |a Output Types/Journal article
|2 DataCite
336 7 _ |a Journal Article
|0 0
|2 EndNote
336 7 _ |a ARTICLE
|2 BibTeX
336 7 _ |a JOURNAL_ARTICLE
|2 ORCID
336 7 _ |a article
|2 DRIVER
440 _ 0 |0 11862
|a Hepatology
|v 53
|x 0270-9139
|y 4
500 _ _ |a Supported 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.
520 _ _ |a 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.
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|a Funktion und Dysfunktion des Nervensystems
|c P33
|x 0
536 _ _ |0 G:(DE-Juel1)FUEK505
|2 G:(DE-HGF)
|a BioSoft: Makromolekulare Systeme und biologische Informationsverarbeitung
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588 _ _ |a Dataset connected to Web of Science, Pubmed
650 _ 2 |2 MeSH
|a Benzoquinones: pharmacology
650 _ 2 |2 MeSH
|a Cell Line, Tumor
650 _ 2 |2 MeSH
|a Hepacivirus: genetics
650 _ 2 |2 MeSH
|a Hepacivirus: physiology
650 _ 2 |2 MeSH
|a Humans
650 _ 2 |2 MeSH
|a Lactams, Macrocyclic: pharmacology
650 _ 2 |2 MeSH
|a RNA Replicase: genetics
650 _ 2 |2 MeSH
|a Viral Nonstructural Proteins
650 _ 2 |2 MeSH
|a Virus Replication
650 _ 2 |2 MeSH
|a src Homology Domains: genetics
650 _ 2 |2 MeSH
|a src-Family Kinases: physiology
650 _ 7 |0 0
|2 NLM Chemicals
|a Benzoquinones
650 _ 7 |0 0
|2 NLM Chemicals
|a Lactams, Macrocyclic
650 _ 7 |0 0
|2 NLM Chemicals
|a NS-5 protein, hepatitis C virus
650 _ 7 |0 0
|2 NLM Chemicals
|a Viral Nonstructural Proteins
650 _ 7 |0 70563-58-5
|2 NLM Chemicals
|a herbimycin
650 _ 7 |0 EC 2.7.10.2
|2 NLM Chemicals
|a src-Family Kinases
650 _ 7 |0 EC 2.7.7.48
|2 NLM Chemicals
|a RNA Replicase
650 _ 7 |2 WoSType
|a J
700 1 _ |0 P:(DE-Juel1)VDB98447
|a Büther, K.
|b 1
|u FZJ
700 1 _ |0 P:(DE-Juel1)VDB98448
|a Karthe, J.
|b 2
|u FZJ
700 1 _ |0 P:(DE-Juel1)VDB98449
|a Poenisch, M.
|b 3
|u FZJ
700 1 _ |0 P:(DE-Juel1)VDB98450
|a Bartenschlager, R.
|b 4
|u FZJ
700 1 _ |0 P:(DE-Juel1)VDB98451
|a Trilling, M.
|b 5
|u FZJ
700 1 _ |0 P:(DE-Juel1)VDB98452
|a Hengel, H.
|b 6
|u FZJ
700 1 _ |0 P:(DE-Juel1)132029
|a Willbold, D.
|b 7
|u FZJ
700 1 _ |0 P:(DE-Juel1)VDB9577
|a Häussinger, D.
|b 8
|u FZJ
700 1 _ |0 P:(DE-Juel1)VDB98456
|a Bode, J. G.
|b 9
|u FZJ
773 _ _ |0 PERI:(DE-600)1472120-x
|a 10.1002/hep.24214
|g Vol. 53, p. 1127 - 1136
|p 1127 - 1136
|q 53<1127 - 1136
|t Hepatology
|v 53
|x 0270-9139
|y 2011
856 7 _ |u http://dx.doi.org/10.1002/hep.24214
909 C O |o oai:juser.fz-juelich.de:15093
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913 1 _ |0 G:(DE-Juel1)FUEK409
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914 1 _ |y 2011
915 _ _ |0 StatID:(DE-HGF)0010
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920 1 _ |0 I:(DE-Juel1)ICS-6-20110106
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