title: Interferon-inducible protein SCOTIN interferes with HCV replication through the autolysosomal degradation of NS5A.
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.
authors: Division of Molecular and Life Sciences, Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
authors: Nari
authors: N
authors: Kim
authors: Division of Molecular and Life Sciences, Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
authors: Min-Jung
authors: MJ
authors: Kim
authors: Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon 305-701, Republic of Korea.
authors: Pil Soo
authors: PS
authors: Sung
authors: Department of Anatomy and Neurobiology, School of Dentistry, Kyungpook National University, Daegu 41940, Republic of Korea.
authors: Yong Chul
authors: YC
authors: Bae
authors: Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon 305-701, Republic of Korea.
authors: Eui-Cheol
authors: EC
authors: Shin
authors: Division of Molecular and Life Sciences, Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
authors: Joo-Yeon
authors: JY
authors: Yoo
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000276:immunology*; D001343:Autophagy / Q000276:immunology*; D045744:Cell Line, Tumor; D005455:Fluorescent Antibody Technique; D016174:Hepacivirus / Q000378:metabolism* / Q000502:physiology; D022781:Hepatocytes; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D016899:Interferon-beta / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology*; D010588:Phagosomes / Q000276:immunology*; D012367:RNA, Viral / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D014779:Virus Replication / Q000502:physiology*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D051017:Apoptosis Regulatory Proteins; D016899:Interferon-beta; D008565:Membrane Proteins; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; C462779:SHISA5 protein, human; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase