Interferon-inducible protein SCOTIN interferes with HCV replication through the autolysosomal degradation of NS5A
SCIE
SCOPUS
- Title
- Interferon-inducible protein SCOTIN interferes with HCV replication through the autolysosomal degradation of NS5A
- Authors
- Nari Kim; Min-Jung Kim; Pil Soo Sung; Yong Chul Bae; Eui-Cheol Shin; Yoo, JY
- Date Issued
- 2016-02
- Publisher
- Nature Publishing Group
- 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-beta-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-beta-induced SCOTIN recruits the HCV NS5A protein to autophagosomes for degradation, thereby restricting HCV replication.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/35981
- DOI
- 10.1038/NCOMMS10631
- ISSN
- 2041-1723
- Article Type
- Article
- Citation
- Nature Communications, vol. 7, page. 10631, 2016-02
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