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

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 cul...

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Autores principales: Kim, Nari, Kim, Min-Jung, Sung, Pil Soo, Bae, Yong Chul, Shin, Eui-Cheol, Yoo, Joo-Yeon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754343/
https://www.ncbi.nlm.nih.gov/pubmed/26868272
http://dx.doi.org/10.1038/ncomms10631
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author Kim, Nari
Kim, Min-Jung
Sung, Pil Soo
Bae, Yong Chul
Shin, Eui-Cheol
Yoo, Joo-Yeon
author_facet Kim, Nari
Kim, Min-Jung
Sung, Pil Soo
Bae, Yong Chul
Shin, Eui-Cheol
Yoo, Joo-Yeon
author_sort Kim, Nari
collection PubMed
description 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.
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spelling pubmed-47543432016-03-04 Interferon-inducible protein SCOTIN interferes with HCV replication through the autolysosomal degradation of NS5A Kim, Nari Kim, Min-Jung Sung, Pil Soo Bae, Yong Chul Shin, Eui-Cheol Yoo, Joo-Yeon Nat Commun Article 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. Nature Publishing Group 2016-02-12 /pmc/articles/PMC4754343/ /pubmed/26868272 http://dx.doi.org/10.1038/ncomms10631 Text en Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Kim, Nari
Kim, Min-Jung
Sung, Pil Soo
Bae, Yong Chul
Shin, Eui-Cheol
Yoo, Joo-Yeon
Interferon-inducible protein SCOTIN interferes with HCV replication through the autolysosomal degradation of NS5A
title Interferon-inducible protein SCOTIN interferes with HCV replication through the autolysosomal degradation of NS5A
title_full Interferon-inducible protein SCOTIN interferes with HCV replication through the autolysosomal degradation of NS5A
title_fullStr Interferon-inducible protein SCOTIN interferes with HCV replication through the autolysosomal degradation of NS5A
title_full_unstemmed Interferon-inducible protein SCOTIN interferes with HCV replication through the autolysosomal degradation of NS5A
title_short Interferon-inducible protein SCOTIN interferes with HCV replication through the autolysosomal degradation of NS5A
title_sort interferon-inducible protein scotin interferes with hcv replication through the autolysosomal degradation of ns5a
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754343/
https://www.ncbi.nlm.nih.gov/pubmed/26868272
http://dx.doi.org/10.1038/ncomms10631
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