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@ARTICLE{Pfannkuche:15093,
author = {Pfannkuche, A. and Büther, K. and Karthe, J. and Poenisch,
M. and Bartenschlager, R. and Trilling, M. and Hengel, H.
and Willbold, D. and Häussinger, D. and Bode, J. G.},
title = {{C}-{S}rc is required for complex formation between the
hepatitis {C} virus–encoded proteins {NS}5{A} and
{NS}5{B}: {A} prerequisite for replication},
journal = {Hepatology},
volume = {53},
issn = {0270-9139},
address = {New York [u.a.]},
publisher = {Wiley Interscience},
reportid = {PreJuSER-15093},
pages = {1127 - 1136},
year = {2011},
note = {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.},
abstract = {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.},
keywords = {Benzoquinones: pharmacology / Cell Line, Tumor /
Hepacivirus: genetics / Hepacivirus: physiology / Humans /
Lactams, Macrocyclic: pharmacology / RNA Replicase: genetics
/ Viral Nonstructural Proteins / Virus Replication / src
Homology Domains: genetics / src-Family Kinases: physiology
/ Benzoquinones (NLM Chemicals) / Lactams, Macrocyclic (NLM
Chemicals) / NS-5 protein, hepatitis C virus (NLM Chemicals)
/ Viral Nonstructural Proteins (NLM Chemicals) / herbimycin
(NLM Chemicals) / src-Family Kinases (NLM Chemicals) / RNA
Replicase (NLM Chemicals) / J (WoSType)},
cin = {ICS-6},
ddc = {610},
cid = {I:(DE-Juel1)ICS-6-20110106},
pnm = {Funktion und Dysfunktion des Nervensystems / BioSoft:
Makromolekulare Systeme und biologische
Informationsverarbeitung},
pid = {G:(DE-Juel1)FUEK409 / G:(DE-Juel1)FUEK505},
shelfmark = {Gastroenterology $\&$ Hepatology},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:21480319},
UT = {WOS:000289419600008},
doi = {10.1002/hep.24214},
url = {https://juser.fz-juelich.de/record/15093},
}