title: EPSTI1 Is Involved in IL-28A-Mediated Inhibition of HCV Infection.
abstract: It has been reported that IFN-λs inhibit HCV replication in vitro. But the mechanisms of how IL-28A conducts antiviral activity and the functions of IL-28A-induced ISGs (IFN-stimulated genes) are not fully understood. In this study, we found that IL-28A has the antiviral effect on HCV life cycle including viral replication, assembly, and release. IL-28A and IFN-α synergistically inhibit virus replication. EPSTI1 (epithelial-stromal interaction 1), one of IL-28A-induced ISGs, plays a vital role in IL-28A-mediated antiviral activity. Furthermore, forced expression of EPSTI1 effectively inhibits HCV replication in the absence of interferon treatment, and knockdown of EPSTI1 contributes to viral enhancement. EPSTI1 can activate PKR promoter and induce several PKR-dependent genes, including IFN-β, IFIT1, OAS1, and RNase L, which is responsible for EPSTI1-mediated antiviral activity.
authors.affiliation: Department of Molecular Medicine of College of Biology, State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan University, Changsha 410082, China.
authors.forename: Xianghe
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of Molecular Medicine of College of Biology, State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan University, Changsha 410082, China.
authors.forename: Darong
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Molecular Medicine of College of Biology, State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan University, Changsha 410082, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Yu
authors.affiliation: Department of Molecular Medicine of College of Biology, State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan University, Changsha 410082, China ; Research Center of Cancer Prevention & Treatment, Translational Medicine Research Center of Liver Cancer, Hunan Provincial Tumor Hospital, Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha 410013, China.
authors.forename: Haizhen
authors.initials: H
authors.lastname: Zhu
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000502:physiology; D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000502:physiology*; D011401:Promoter Regions, Genetic; D019065:Virus Assembly / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects; D019892:eIF-2 Kinase / Q000235:genetics / Q000502:physiology; D000095022:Interferon Lambda
chemical_list: D015088:2',5'-Oligoadenylate Synthetase; D000998:Antiviral Agents; D016898:Interferon-alpha; D007378:Interleukins; D009363:Neoplasm Proteins; D019892:eIF-2 Kinase; C459199:EPSTI1 protein, human; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C475085:OAS1 protein, human