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Sci Rep. 2015 Sep 1;5:13344. doi: 10.1038/srep13344.

PI4K-beta and MKNK1 are regulators of hepatitis C virus IRES-dependent translation.

Author information

1
Inserm U1110, Institut de Recherche sur les Maladies Virales et Hépatiques Strasbourg, France.
2
Université de Strasbourg, France.
3
Department of Medicine II, University of Freiburg, Freiburg, Germany.
4
High Throughput Screening platform, IGBMC, UMR7104 CNRS UdS, Inserm, U964, Illkirch, France.
5
Laboratory of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan.
6
Institut Hospitalo-Universitaire, Pôle Hépato-digestif, Nouvel Hôpital Civil, Strasbourg, France.

Abstract

Cellular translation is down-regulated by host antiviral responses. Picornaviridae and Flaviviridae including hepatitis C virus (HCV) evade this process using internal ribosomal entry sequences (IRESs). Although HCV IRES translation is a prerequisite for HCV replication, only few host factors critical for IRES activity are known and the global regulator network remains largely unknown. Since signal transduction is an import regulator of viral infections and the host antiviral response we combined a functional RNAi screen targeting the human signaling network with a HCV IRES-specific reporter mRNA assay. We demonstrate that the HCV host cell cofactors PI4K and MKNK1 are positive regulators of HCV IRES translation representing a novel pathway with a functional relevance for the HCV life cycle and IRES-mediated translation of viral RNA.

PMID:
26323588
PMCID:
PMC4555030
DOI:
10.1038/srep13344
[Indexed for MEDLINE]
Free PMC Article

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