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

Author

Listed:
  • Nari Kim

    (Pohang University of Science and Technology)

  • Min-Jung Kim

    (Pohang University of Science and Technology)

  • Pil Soo Sung

    (Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST)

  • Yong Chul Bae

    (School of Dentistry, Kyungpook National University)

  • Eui-Cheol Shin

    (Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST)

  • Joo-Yeon Yoo

    (Pohang University of Science and Technology)

Abstract

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-β-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-β-induced SCOTIN recruits the HCV NS5A protein to autophagosomes for degradation, thereby restricting HCV replication.

Suggested Citation

  • Nari Kim & Min-Jung Kim & Pil Soo Sung & Yong Chul Bae & Eui-Cheol Shin & Joo-Yeon Yoo, 2016. "Interferon-inducible protein SCOTIN interferes with HCV replication through the autolysosomal degradation of NS5A," Nature Communications, Nature, vol. 7(1), pages 1-12, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10631
    DOI: 10.1038/ncomms10631
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