Department of Biotechnology, Yonsei University, Seoul, 03722, Korea.
Department of Life Science, Sogang University, Seoul, 04107, Korea.
Nat Commun. 2018 Apr 23;9(1):1606. doi: 10.1038/s41467-018-04075-1.
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.
病原体衍生配体被模式识别受体识别后会激活先天免疫反应，但群体感应（QS）信号分子与宿主抗病毒防御之间的潜在相互作用在很大程度上仍是未知的。在这里，我们发现创伤弧菌的 QS 分子环（苯丙氨酸-脯氨酸）（cFP）通过干扰视黄酸诱导基因-I（RIG-I）的激活来抑制干扰素（IFN）-β的产生。cFP 与 RIG-I 的 2CARD 结构域结合会引起 RIG-I 的构象变化，阻止 TRIM25 介导的泛素化从而阻断 IFN 的产生。cFP 增强了对丙型肝炎病毒（HCV）、仙台病毒和流感病毒的易感性，这些病毒都已知被 RIG-I 识别，但不会影响黑色素瘤分化相关基因 5（MDA5）对诺如病毒的识别。我们的研究结果揭示了细菌、病毒和宿主之间的跨领域网络，通过微生物群体感应分子调节对病毒感染的反应，从而使宿主先天反应失调。
