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

doi:10.1038/s41467-018-04075-1

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.

Authors

Wooseong Lee¹, Seung-Hoon Lee¹, Minwoo Kim¹, Jae-Su Moon¹, Geon-Woo Kim¹, Hae-Gwang Jung¹, In Hwang Kim², Ji Eun Oh³, Hi Eun Jung⁴, Heung Kyu Lee^{3

4}, Keun Bon Ku⁵, Dae-Gyun Ahn⁵, Seong-Jun Kim⁵, Kun-Soo Kim², Jong-Won Oh⁶

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].

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line, Tumor
DEAD Box Protein 58 / immunology
DEAD Box Protein 58 / metabolism*
Dipeptides / immunology*
Disease Models, Animal
HEK293 Cells
Hepatocytes
Host-Pathogen Interactions / immunology*
Humans
Immunity, Innate / drug effects*
Interferon-beta / immunology
Interferon-beta / metabolism
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Inbred NOD
Mice, SCID
Peptides, Cyclic / immunology*
Primary Cell Culture
Quorum Sensing / immunology*
RAW 264.7 Cells
RNA Virus Infections / immunology
RNA Virus Infections / microbiology
RNA Viruses / immunology
RNA Viruses / pathogenicity
Receptors, Immunologic
Signal Transduction / drug effects
Signal Transduction / immunology
Superinfection / immunology
Superinfection / microbiology
Vibrio Infections / immunology
Vibrio Infections / microbiology
Vibrio vulnificus / immunology

Substances

Dipeptides
Peptides, Cyclic
Receptors, Immunologic
cyclo(phenylalanyl-prolyl)
Interferon-beta
RIGI protein, human
DEAD Box Protein 58