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Int. J. Mol. Sci. 2014, 15(10), 19281-19306; doi:10.3390/ijms151019281

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

1
Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 11574, Taiwan
2
Department of Basic Sciences and Aquatic Medicine, Norwegian University of Life Sciences, Oslo 0454, Norway
3
Institute of Biotechnology, National Cheng-Kung University, Tainan 70101, Taiwan
4
Department of Aquaculture, National Taiwan Ocean University, Keelung 20224, Taiwan
5
Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung 20224, Taiwan
*
Authors to whom correspondence should be addressed.
Received: 13 May 2014 / Revised: 13 October 2014 / Accepted: 14 October 2014 / Published: 23 October 2014
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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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. View Full-Text
Keywords: phosphatidylserine receptor (PSR); interferon regulatory factor-1 (IRF-1); interferon (IFN); apoptosis phosphatidylserine receptor (PSR); interferon regulatory factor-1 (IRF-1); interferon (IFN); apoptosis
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Kung, H.-C.; Evensen, Ø.; Hong, J.-R.; Kuo, C.-Y.; Tso, C.-H.; Ngou, F.-H.; Lu, M.-W.; Wu, J.-L. 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. Int. J. Mol. Sci. 2014, 15, 19281-19306.

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