Lee, Na-Rae Ban, Junsu Lee, Noh-Jin Yi, Chae-Min Choi, Ji-Yoon Kim, Hyunbin Lee, Jong Kil Seong, Jihye Cho, Nam-Hyuk Jung, Jae U. Inn, Kyung-Soo 2024-01-19T22:00:30Z 2024-01-19T22:00:30Z 2021-09-03 2018-09-12 1664-3224 https://pubs.kist.re.kr/handle/201004/120916 Autophagy has been implicated in innate immune responses against various intracellular pathogens. Recent studies have reported that autophagy can be triggered by pathogen recognizing sensors, including Toll-like receptors and cyclic guanosine monophosphate-adenosine monophosphate synthase, to participate in innate immunity. In the present study, we examined whether the RIG-I signaling pathway, which detects viral infections by recognizing viral RNA, triggers the autophagic process. The introduction of polyI:C into the cytoplasm, or Sendai virus infection, significantly induced autophagy in normal cells but not in RIG-I-deficient cells. PolyI:C transfection or Sendai virus infection induced autophagy in the cells lacking type-I interferon signaling. This demonstrated that the effect was not due to interferon signaling. RIG-I-mediated autophagy diminished by the deficiency of mitochondrial antiviral signaling protein (MAVS) or tumor necrosis factor receptor-associated factor (TRAF)6, showing that the RIG-I-MAVS-TRAF6 signaling axis was critical for RIG-I-mediated autophagy. We also found that Beclin-1 was translocated to the mitochondria, and it interacted with TRAF6 upon RIG-I activation. Furthermore, Beclin-1 underwent K63-polyubiquitination upon RIGI activation, and the ubiquitination decreased in TRAF6-deficient cells. This suggests that the RIG-I-MAVS-TRAF6 axis induced K63-linked polyubiquitination of Beclin-1, which has been implicated in triggering autophagy. As deficient autophagy increases the type-I interferon response, the induction of autophagy by the RIG-I pathway might also contribute to preventing an excessive interferon response as a negative-feedback mechanism. English FRONTIERS MEDIA SA PATTERN-RECOGNITION RECEPTORS IMMUNE-RESPONSES CELLULAR AUTOPHAGY INNATE IMMUNITY BECLIN 1 NDP52 DNA PHOSPHORYLATION UBIQUITINATION INFLAMMATION Activation of RIG-I-Mediated Antiviral Signaling Triggers Autophagy Through the MAVS-TRAF6-Beclin-1 Signaling Axis Article 10.3389/fimmu.2018.02096 1 FRONTIERS IN IMMUNOLOGY, v.9 FRONTIERS IN IMMUNOLOGY 9 scie scopus 000444423700001 2-s2.0-85053160931 Immunology Immunology Article PATTERN-RECOGNITION RECEPTORS IMMUNE-RESPONSES CELLULAR AUTOPHAGY INNATE IMMUNITY BECLIN 1 NDP52 DNA PHOSPHORYLATION UBIQUITINATION INFLAMMATION autophagy RIG-I MAVS TRAF6 polyubiquitination Beclin-1 innate immunity