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Cell Rep. 2019 May 14;27(7):2105-2118.e5. doi: 10.1016/j.celrep.2019.04.071.

Small Heterodimer Partner Controls the Virus-Mediated Antiviral Immune Response by Targeting CREB-Binding Protein in the Nucleus.

Author information

1
College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea; Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, University of Science and Technology (UST), Daejeon, Republic of Korea.
2
College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea.
3
College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea; Faculty of Veterinary & Animal Science, Sylhet Agricultural University, Sylhet-3100, Bangladesh.
4
Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, University of Science and Technology (UST), Daejeon, Republic of Korea.
5
National Creative Research Initiatives Center for Nuclear Receptor Signals and Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju, Republic of Korea.
6
Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
7
Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, University of Science and Technology (UST), Daejeon, Republic of Korea. Electronic address: chullee@kribb.re.kr.
8
College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea. Electronic address: jongsool@cnu.ac.kr.

Abstract

Small heterodimer partner (SHP) is an orphan nuclear receptor that acts as a transcriptional co-repressor by interacting with nuclear receptors and transcription factors. Although SHP plays a negative regulatory function in various signaling pathways, its role in virus infection has not been studied. Here, we report that SHP is a potent negative regulator of the virus-mediated type I IFN signaling that maintains homeostasis within the antiviral innate immune system. Upon virus infection, SHP interacts specifically with CREB-binding protein (CBP) in the nucleus, thereby obstructing CBP/β-catenin interaction competitively. Consequently, SHP-deficient cells enhance antiviral responses, including transcription of the type I IFN gene, upon virus infection. Furthermore, SHP-deficient mice show higher levels of IFN production and are more resistant to influenza A virus infection. Our results suggest that SHP is a nuclear regulator that blocks transcription of the type I IFN gene to inhibit excessive innate immune responses.

KEYWORDS:

CBP; SHP; type I interferon; β-catenin

PMID:
31091449
DOI:
10.1016/j.celrep.2019.04.071
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