title: Interferon regulatory factor-1 (IRF-1) is involved in the induction of phosphatidylserine receptor (PSR) in response to dsRNA virus infection and contributes to apoptotic cell clearance in CHSE-214 cell.
abstract: The phosphatidylserine receptor (PSR) recognizes a surface marker on apoptotic cells and initiates engulfment. This receptor is important for effective apoptotic cell clearance and maintains normal tissue homeostasis and regulation of the immune response. However, the regulation of PSR expression remains poorly understood. In this study, we determined that interferon regulatory factor-1 (IRF-1) was dramatically upregulated upon viral infection in the fish cell. We observed apoptosis in virus-infected cells and found that both PSR and IRF-1 increased simultaneously. Based on a bioinformatics promoter assay, IRF-1 binding sites were identified in the PSR promoter. Compared to normal viral infection, we found that PSR expression was delayed, viral replication was increased and virus-induced apoptosis was inhibited following IRF-1 suppression with morpholino oligonucleotides. A luciferase assay to analyze promoter activity revealed a decreasing trend after the deletion of the IRF-1 binding site on PSR promoter. The results of this study indicated that infectious pancreatic necrosis virus (IPNV) infection induced both the apoptotic and interferon (IFN) pathways, and IRF-1 was involved in regulating PSR expression to induce anti-viral effects. Therefore, this work suggests that PSR expression in salmonid cells during IPNV infection is activated when IRF-1 binds the PSR promoter. This is the first report to show the potential role of IRF-1 in triggering the induction of apoptotic cell clearance-related genes during viral infection and demonstrates the extensive crosstalk between the apoptotic and innate immune response pathways.
authors.affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 11574, Taiwan. znga.hg@gmail.com.
authors.forename: Hsin-Chia
authors.initials: HC
authors.lastname: Kung
authors.affiliation: Department of Basic Sciences and Aquatic Medicine, Norwegian University of Life Sciences, Oslo 0454, Norway. oystein.evensen@nmbu.no.
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Evensen
authors.affiliation: Institute of Biotechnology, National Cheng-Kung University, Tainan 70101, Taiwan. jrhong@mail.ncku.edu.tw.
authors.forename: Jiann-Ruey
authors.initials: JR
authors.lastname: Hong
authors.affiliation: Department of Aquaculture, National Taiwan Ocean University, Keelung 20224, Taiwan. key33_40@hotmail.com.
authors.forename: Chia-Yu
authors.initials: CY
authors.lastname: Kuo
authors.affiliation: Department of Aquaculture, National Taiwan Ocean University, Keelung 20224, Taiwan. chunhsi.tso@hotmail.com.
authors.forename: Chun-Hsi
authors.initials: CH
authors.lastname: Tso
authors.affiliation: Department of Aquaculture, National Taiwan Ocean University, Keelung 20224, Taiwan. fanghuar@hotmail.com.
authors.forename: Fang-Huar
authors.initials: FH
authors.lastname: Ngou
authors.affiliation: Department of Aquaculture, National Taiwan Ocean University, Keelung 20224, Taiwan. mingwei@ntou.edu.tw.
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Lu
authors.affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 11574, Taiwan. jlwu@gate.sinica.edu.tw.
authors.forename: Jen-Leih
authors.initials: JL
authors.lastname: Wu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics / Q000276:immunology; D018175:Birnaviridae Infections / Q000235:genetics* / Q000276:immunology; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D005399:Fishes; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D018061:Infectious pancreatic necrosis virus / Q000276:immunology; D050856:Interferon Regulatory Factor-1 / Q000235:genetics* / Q000276:immunology; D007372:Interferons / Q000276:immunology; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000276:immunology; D012328:RNA Viruses / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000276:immunology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology; D014779:Virus Replication / Q000235:genetics / Q000276:immunology
chemical_list: D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; D011956:Receptors, Cell Surface; C408123:phosphatidylserine receptor; D007372:Interferons