Why the study?
Does MKNK1 inhibition reduce HCV IRES-dependent translation and HCV infection in hepatoma cell lines?
Does MKNK1 inhibition reduce HCV IRES-dependent translation and HCV infection in hepatoma cell lines?
PI4K-beta and MKNK1 are identified as positive regulators of HCV IRES translation, presenting potential novel antiviral targets.
Preclinical MKNK1 inhibition supports HCV IRES targeting in cell models; leaves open clinical translation pending in vivo and human studies.
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.
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Lupberger et al. (2015) studied this question.
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