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

Wooseong Lee, Seung Hoon Lee, Minwoo Kim, Jae Su Moon, Geon Woo Kim, Hae Gwang Jung, In Hwang Kim, Ji Eun Oh, Hi Eun Jung, Heung Kyu Lee, Keun Bon Ku, Dae Gyun Ahn, Seong Jun Kim, Kun Soo Kim, Jong Won Oh

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14 Citations (Scopus)

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.

Original languageEnglish
Article number1606
JournalNature communications
Volume9
Issue number1
DOIs
Publication statusPublished - 2018 Dec 1

Bibliographical note

Funding Information:
We thank Drs. Takaji Wakita (National Institute of Infectious Diseases, Japan), Xulin Chen (Institute for Virus Research, Chinese Academic of Sciences, China), John Hiscott (McGill University, Montreal, Quebec, Canada), Herbert W. Virgin (Washington University School of Medicine, St. Louis, USA), Frank Chisari (Scripps Research Institute, La Jolla, CA, USA), Christoph Seeger (Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA, USA), and Jong-Bok Yoon (Yonsei University, Seoul, Korea) for reagents. This work was supported by grants from the National Research Foundation of Korea funded by the Korean government (MSIP) (2014R1A2A2A01005522, 2016R1A5A1004694, and COMPA 2015-11-1670) and in part by the NRF grant NRF- 2017R1A2B2006966 to K.-S.K. and the National Research Council of Science & Technology (NST) grant CRC-16-01-KRICT to S.-J.K. W.L. was the recipient of a postdoctoral fellowship (2017-12-0035) from Yonsei University. S.-H.L., M.K., J.-S.M., G.-W.K., and H.-G.J. were in part supported by the BK21 PLUS program.

Funding Information:
We thank Drs. Takaji Wakita (National Institute of Infectious Diseases, Japan), Xulin Chen (Institute for Virus Research, Chinese Academic of Sciences, China), John Hiscott (McGill University, Montreal, Quebec, Canada), Herbert W. Virgin (Washington University School of Medicine, St. Louis, USA), Frank Chisari (Scripps Research Institute, La Jolla, CA, USA), Christoph Seeger (Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA, USA), and Jong-Bok Yoon (Yonsei University, Seoul, Korea) for reagents. This work was supported by grants from the National Research Foundation of Korea funded by the Korean government (MSIP) (2014R1A2A2A01005522, 2016R1A5A1004694, and COMPA 2015-11-1670) and in part by the NRF grant NRF-2017R1A2B2006966 to K.-S.K. and the National Research Council of Science & Technology (NST) grant CRC-16-01-KRICT to S.-J.K. W.L. was the recipient of a postdoctoral fellowship (2017-12-0035) from Yonsei University. S.-H.L., M.K., J.-S.M., G.-W.K., and H.-G.J. were in part supported by the BK21 PLUS program.

Publisher Copyright:
© 2018 The Author(s).

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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