Vibrio vulnificus quorum-sensing molecule cyclo(Phe-Pro) inhibits RIG-I-mediated antiviral innate immunity

  • Nat Commun. 2018 Apr 23;9(1):1606. doi: 10.1038/s41467-018-04075-1.
Wooseong Lee  1 ,  Seung-Hoon Lee  1 ,  Minwoo Kim  1 ,  Jae-Su Moon  1 ,  Geon-Woo Kim  1 ,  Hae-Gwang Jung  1 ,  In Hwang Kim  2 ,  Ji Eun Oh  3 ,  Hi Eun Jung  4 ,  Heung Kyu Lee  3  4 ,  Keun Bon Ku  5 ,  Dae-Gyun Ahn  5 ,  Seong-Jun Kim  5 ,  Kun-Soo Kim  2 ,  Jong-Won Oh  6
Affiliations
  • 1. Department of Biotechnology, Yonsei University, Seoul, 03722, Korea.
  • 2. Department of Life Science, Sogang University, Seoul, 04107, Korea.
  • 3. Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Korea.
  • 4. Biomedical Science and Engineering Interdisciplinary Program, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Korea.
  • 5. Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon, 34114, Korea.
  • 6. Department of Biotechnology, Yonsei University, Seoul, 03722, Korea. [email protected].
PMID: 29686409 DOI: 10.1038/s41467-018-04075-1
Abstract

The recognition of pathogen-derived ligands by Pattern Recognition Receptors activates the innate immune response, but the potential interaction of quorum-sensing (QS) signaling molecules with host anti-viral defenses remains largely unknown. Here we show that the Vibrio vulnificus QS molecule cyclo(Phe-Pro) (cFP) inhibits interferon (IFN)-β production by interfering with retinoic-acid-inducible gene-I (RIG-I) activation. Binding of cFP to the RIG-I 2CARD domain induces a conformational change in RIG-I, preventing the TRIM25-mediated ubiquitination to abrogate IFN production. cFP enhances susceptibility to hepatitis C virus (HCV), as well as Sendai and influenza viruses, each known to be sensed by RIG-I but did not affect the melanoma-differentiation-associated gene 5 (MDA5)-recognition of norovirus. Our results reveal an inter-kingdom network between bacteria, viruses and host that dysregulates host innate responses via a microbial quorum-sensing molecule modulating the response to viral Infection.

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