Interferon-inducible protein SCOTIN interferes with HCV replication through the autolysosomal degradation of NS5A > 연구성과

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Interferon-inducible protein SCOTIN interferes with HCV replication th…

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  • 저널명Nat Commun. 2016 Feb 12;7:10631. doi: 10.1038/ncomms10631.
    • 담당교수[2016년 2월] 유주연 교수연구실
    • 조회1,445
    • 작성자최고관리자
    • 2017-10-23


    Hepatitis C virus (HCV) utilizes autophagy to promote its propagation. Here we show the
    autophagy-mediated suppression of HCV replication via the endoplasmic reticulum (ER)
    protein SCOTIN. SCOTIN overexpression inhibits HCV replication and infectious virion
    production in cells infected with cell culture-derived HCV. HCV nonstructural 5A (NS5A)
    protein, which is a critical factor for HCV RNA replication, interacts with the IFN-b-inducible
    protein SCOTIN, which transports NS5A to autophagosomes for degradation. Furthermore,
    the suppressive effect of SCOTIN on HCV replication is impaired in both ATG7-silenced cells
    and cells treated with autophagy or lysosomal inhibitors. SCOTIN does not affect the overall
    flow of autophagy; however, it is a substrate for autophagic degradation. The physical
    association between the transmembrane/proline-rich domain (TMPRD) of SCOTIN and
    Domain-II of NS5A is essential for autophagosomal trafficking and NS5A degradation.
    Altogether, our findings suggest that IFN-b-induced SCOTIN recruits the HCV NS5A protein
    to autophagosomes for degradation, thereby restricting HCV replication.
    DOI: 10.1038/ncomms10631 OPEN

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