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Cited 59 time in webofscience Cited 61 time in scopus
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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 KimMin-Jung KimPil Soo SungYong Chul BaeEui-Cheol ShinYoo, 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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