Activation of RIG-I-mediated antiviral signaling triggers autophagy through the MAVS-TRAF6-Beclin-1 signaling axis

Title
Activation of RIG-I-mediated antiviral signaling triggers autophagy through the MAVS-TRAF6-Beclin-1 signaling axis
Authors
성지혜김현빈Na-Rae LeeJunsu BanNoh-Jin LeeChae-Min YiJi-Yoon ChoiJong Kil LeeNam-Hyuk ChoJae U. JungKyung-Soo Inn
Issue Date
2018-09
Publisher
Frontiers in Immunology
Citation
VOL 9-2096-14
Abstract
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.
URI
http://pubs.kist.re.kr/handle/201004/68301
ISSN
1664-3224
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KIST Publication > Article
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