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

Nari Kim, Min-Jung Kim, Pil Soo Sung, Yong Chul Bae, Eui-Cheol Shin and Joo-Yeon Yoo ()
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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

Nature Communications, 2016, vol. 7, issue 1, 1-12

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms10631

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