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

Jae Hoon Kim, Ji Eun Yoon, Chamilani Nikapitiya, Tae Hwan Kim, Md Bashir Uddin, Hyun Cheol Lee, Yong Hoon Kim, Jung Hwan Hwang, Kiramage Chathuranga, W. A.Gayan Chathuranga, Hueng Sik Choi, Chul Joong Kim, Jae U. Jung, Chul Ho Lee, Jong Soo Lee

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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. Interferon (IFN), which has an antiviral effect, must be tightly modulated to prevent excessive induction that adversely affects the host. Kim et al. demonstrate that SHP acts as negative regulator of type I IFN signaling, which inhibits IFN gene transcription by blocking the interaction of CBP and β-catenin.

Original languageEnglish (US)
Pages (from-to)2105-2118.e5
JournalCell Reports
Volume27
Issue number7
DOIs
StatePublished - May 14 2019
Externally publishedYes

Keywords

  • CBP
  • SHP
  • type I interferon
  • β-catenin

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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