Hokkaido University · Medicine
Professor Naoya Sakamoto's research lab focuses on viral immune evasion mechanisms, particularly those employed by hepatitis C virus (HCV) to subvert host innate immune responses. The lab investigates how HCV proteins such as NS5B, NS4B, and others interfere with key signaling pathways like RIG-I/STING and IFN-Jak/STAT, thereby suppressing interferon production and antiviral gene expression. A central theme is identifying viral-host protein interactions that enable viral persistence, with translational applications in developing novel antiviral therapies targeting these immune escape mechanisms. The lab also explores RNA-targeting therapeutics, such as ribozymes, to directly inhibit HCV replication at the genetic level.
Figures are computed from collected data and may differ slightly.
Binding of the HCV-NS5B protein to GBP-1 countered the antiviral effect by inhibition of its GTPase activity. These mechanisms may contribute to resistance to innate, IFN-mediated antiviral defense and to the clinical persistence of HCV infection.
NS4B suppresses RIG-I-mediated IFN-β production signaling through a direct protein interaction with STING. Disruption of that interaction may restore cellular antiviral responses and may constitute a novel therapeutic strategy for the eradication of HCV.
To determine the effects of hammerhead ribozymes against hepatitis C virus (HCV) RNA on viral protein translation, a luciferase reporter gene vector, pCMV/T7-NCRCdelta-luc, was constructed containing the 5'-noncoding region (5'-NCR) and part of the core region of HCV. Four ribozymes, Rz1-Rz4, were designed to cleave at nucleotide positions 136-160, 313-337, 496-520, and 373-388, respectively. Each ribozyme cleaved the target RNA at expected positions under cell-free conditions. Rz2 and Rz4 signi
Cellular antiviral responses are mediated partly by the expression of interferon-stimulated genes, triggered by viral genomes, their transcripts and replicative intermediates. Persistent replication of a hepatitis C virus (HCV) replicon suggests that the replicon does not elicit cellular innate antiviral responses. In the present study, we investigated regulatory factors of the interferon-mediated antiviral system in cells expressing an HCV replicon. Luciferase reporter assays revealed that the
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