title: Suppression of dual specificity phosphatase I expression inhibits hepatitis C virus replication.
abstract: It was reported that dual specificity phosphatase 1 (DUSP1) is specifically upregulated in the liver of patients with chronic hetpatitis C virus (HCV) infection who do not respond to peginterferon (PegIFN) treatment. Here, we have investigated the role of DUSP1 in HCV replication in hepatoma cells stably expressing the full HCV replicon (FK). DUSP1 was silenced in cells harboring the FK replicon using a lentiviral vector encoding a DUSP1-specific short hairpin RNA (LV-shDUSP1). We demonstrated that knock-down of DUSP1 significantly inhibited HCV RNA and protein expression. Also, DUSP1 silencing enhanced the expression of phosphorylated signal transducer and activator of transcription 1 (phosho-STAT1) and facilitated the translocation of STAT1 into the nucleus. The mRNA expression levels of myxovirus resistance protein A (MxA), 2'-5'-oligoadenylate synthetase 1 (OAS1), ISG15 ubiquitin-like modifier (ISG15), chemokine C-X-C motif ligand 10 (CXCL10), and ubiquitin-specific protease 18 (USP18) were also accelerated by silencing of DUSP1. Furthermore, combined with the IFN treatment, DUSP1 silencing synergistically decreased the levels of HCV RNA. These results suggest that suppression of DUSP1 expression enhances phosphorylation and nuclear translocation of STAT1, resulting in increasing expression of interferon-stimulated genes (ISGs), which synergizes with IFN's antiviral effect against HCV. In conclusion, DUSP1 is involved in the antiviral host defense mechanism against a HCV infection and thus DUSP1 might be a target to treat chronic HCV infection.
authors: The Catholic University Liver Research Center & WHO Collaborating Center of Hepatitis, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Jung Eun
authors: JE
authors: Choi
authors: The Catholic University Liver Research Center & WHO Collaborating Center of Hepatitis, The Catholic University of Korea, Seoul, Republic of Korea; Department of Internal Medicine, Incheon St. Mary's Hospital, The Catholic University of Korea, Incheon, Republic of Korea.
authors: Jung Hyun
authors: JH
authors: Kwon
authors: The Catholic University Liver Research Center & WHO Collaborating Center of Hepatitis, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Jung-Hee
authors: JH
authors: Kim
authors: The Catholic University Liver Research Center & WHO Collaborating Center of Hepatitis, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Wonhee
authors: W
authors: Hur
authors: Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Republuc of Korea.
authors: Pil Soo
authors: PS
authors: Sung
authors: The Catholic University Liver Research Center & WHO Collaborating Center of Hepatitis, The Catholic University of Korea, Seoul, Republic of Korea; Department of Internal Medicine, St. Paul Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Sang Wook
authors: SW
authors: Choi
authors: The Catholic University Liver Research Center & WHO Collaborating Center of Hepatitis, The Catholic University of Korea, Seoul, Republic of Korea; Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Seung Kew
authors: SK
authors: Yoon
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000473:pathology; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D054638:Dual Specificity Phosphatase 1 / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000235:genetics*; D020868:Gene Silencing; D016174:Hepacivirus / Q000502:physiology*; D006801:Humans; D007372:Interferons / Q000494:pharmacology; D008113:Liver Neoplasms / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D012093:Replicon / Q000235:genetics; D050794:STAT1 Transcription Factor / Q000378:metabolism; D014452:Ubiquitins / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects / Q000235:genetics*
chemical_list: D016207:Cytokines; D034741:RNA, Small Interfering; D050794:STAT1 Transcription Factor; D014452:Ubiquitins; C074034:ISG15 protein, human; D007372:Interferons; D054638:Dual Specificity Phosphatase 1