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Virology. 2014 Aug;462-463:34-41. doi: 10.1016/j.virol.2014.05.016. Epub 2014 Jun 14.

The lysine methyltransferase SMYD3 interacts with hepatitis C virus NS5A and is a negative regulator of viral particle production.

Author information

1
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, AKH BT 25.3, 1090 Vienna, Austria.
2
Department of Infectious Diseases, Molecular Virology, Heidelberg University, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany.
3
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, AKH BT 25.3, 1090 Vienna, Austria; Max-Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
4
Department of Infectious Diseases, Molecular Virology, Heidelberg University, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany; Department of Molecular Medicine, Via Gabelli 63, 35121 Padua, Italy.
5
Department of Infectious Diseases, Molecular Virology, Heidelberg University, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany. Electronic address: Ralf.Bartenschlager@med.uni-heidelberg.de.
6
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, AKH BT 25.3, 1090 Vienna, Austria. Electronic address: gsuperti@cemm.oeaw.ac.at.

Abstract

Hepatitis C virus (HCV) is a considerable global health and economic burden. The HCV nonstructural protein (NS) 5A is essential for the viral life cycle. The ability of NS5A to interact with different host and viral proteins allow it to manipulate cellular pathways and regulate viral processes, including RNA replication and virus particle assembly. As part of a proteomic screen, we identified several NS5A-binding proteins, including the lysine methyltransferase SET and MYND domain containing protein 3 (SMYD3). We confirmed the interaction in the context of viral replication by co-immunoprecipitation and co-localization studies. Mutational analyses revealed that the MYND-domain of SMYD3 and domain III of NS5A are required for the interaction. Overexpression of SMYD3 resulted in decreased intracellular and extracellular virus titers, whilst viral RNA replication remained unchanged, suggesting that SMYD3 negatively affects HCV particle production in a NS5A-dependent manner.

KEYWORDS:

HCV; NS5A; SMYD3; TAP-MS; Virus particle assembly

PMID:
25092459
PMCID:
PMC4139193
DOI:
10.1016/j.virol.2014.05.016
[Indexed for MEDLINE]
Free PMC Article

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