The α isoform of protein kinase CKI is responsible for hepatitis C virus NS5A hyperphosphorylation

Manuela Quintavalle, Sonia Sambucini, Chiara Di Pietro, Raffaele De Francesco, Petra Neddermann

Research output: Contribution to journalArticlepeer-review


Hepatitis C virus (HCV) has been the subject of intensive studies for nearly two decades. Nevertheless, some aspects of the virus life cycle are still a mystery. The HCV nonstructural protein 5A (NS5A) has been shown to be a modulator of cellular processes possibly required for the establishment of viral persistence. NS5A is heavily phosphorylated, and a switch between a basally phosphorylated form of NS5A (p56) and a hyperphosphorylated form of NS5A (p58) seems to play a pivotal role in regulating HCV replication. Using kinase inhibitors that specifically inhibit the formation of NS5A-p58 in cells, we identified the CKI kinase family as a target. NS5A-p58 increased upon overexpression of CKI-α, CKI-δ, and CKI-ε, whereas the RNA interference of only CKI-α reduced NS5A hyperphosphorylation. Rescue of inhibition of NS5A-p58 was achieved by CKI-α overexpression, and we demonstrated that the CKI-α isoform is targeted by NS5A hyperphosphorylation inhibitors in living cells. Finally, we showed that down-regulation of CKI-α attenuates HCV RNA replication.

Original languageEnglish
Pages (from-to)11305-11312
Number of pages8
JournalJournal of Virology
Issue number22
Publication statusPublished - Nov 2006

ASJC Scopus subject areas

  • Immunology


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