Broad and systemic immune-modulating capacity of plant-derived dsRNA

Hajake, Takara; Matsuno, Keita; Kasumba, Dacquin M.; Oda, Hirotaka; Kobayashi, Moe; Miyata, Nao; Shinji, Madoka; Kogure, Akiko; Kasajima, Nodoka; Okamatsu, Masatoshi; Sakoda, Yoshihiro; Kato, Hiroki; Fujita, Takashi

doi:10.1093/intimm/dxz054

Cited by 2 publications

(2 citation statements)

References 69 publications

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“…To investigate the effects of LGP2 on IFN-β induction upon stimulation by different RNA species, we used synthetic RNA poly(I:C), virus (EMCV) and BPEVdsRNA extracted from bell pepper ( 18 ) to stimulate MDA5. HEK293T cells were stimulated as described in (Figure 1A ).…”

Section: Resultsmentioning

confidence: 99%

Viral RNA recognition by LGP2 and MDA5, and activation of signaling through step-by-step conformational changes

Duic

Tadakuma

Harada

et al. 2020

Nucleic Acids Research

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Cytoplasmic RIG-I-like receptor (RLR) proteins in mammalian cells recognize viral RNA and initiate an antiviral response that results in IFN-β induction. Melanoma differentiation-associated protein 5 (MDA5) forms fibers along viral dsRNA and propagates an antiviral response via a signaling domain, the tandem CARD. The most enigmatic RLR, laboratory of genetics and physiology (LGP2), lacks the signaling domain but functions in viral sensing through cooperation with MDA5. However, it remains unclear how LGP2 coordinates fiber formation and subsequent MDA5 activation. We utilized biochemical and biophysical approaches to observe fiber formation and the conformation of MDA5. LGP2 facilitated MDA5 fiber assembly. LGP2 was incorporated into the fibers with an average inter-molecular distance of 32 nm, suggesting the formation of hetero-oligomers with MDA5. Furthermore, limited protease digestion revealed that LGP2 induces significant conformational changes on MDA5, promoting exposure of its CARDs. Although the fibers were efficiently dissociated by ATP hydrolysis, MDA5 maintained its active conformation to participate in downstream signaling. Our study demonstrated the coordinated actions of LGP2 and MDA5, where LGP2 acts as an MDA5 nucleator and requisite partner in the conversion of MDA5 to an active conformation. We revealed a mechanistic basis for LGP2-mediated regulation of MDA5 antiviral innate immune responses.

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Section: Resultsmentioning

confidence: 99%

Viral RNA recognition by LGP2 and MDA5, and activation of signaling through step-by-step conformational changes

Duic

Tadakuma

Harada

et al. 2020

Nucleic Acids Research

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“…Moreover, the OsEV dsRNA treatment in mice suppressed replication of Influenza A virus at an early stages of infection. In another study using BPEV, Hajake et al (2019) reported melanoma-suppressive effects in mice after injecting them with BPEV dsRNA. Furthermore, they found that BPEV dsRNA acted as an effective vaccine adjuvant.…”

Section: Resultsmentioning

confidence: 99%

Effect of two digestive enzymes and pH on the dsRNA of endornaviruses of bell pepper and melon under in vitro conditions

et al. 2019

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Purpose The objective of this investigation was to determine the in vitro effect of two common digestive enzymes, amylase and pepsin, and pH on the integrity of the RI dsRNA of bell pepper endornavirus (BPEV) and Cucumis melo endornavirus (CmEV) evaluated by gel electrophoresis and reverse-transcription PCR (RT-PCR). Methods We conducted experiments on the in vitro effect of two common digestive enzymes, amylase and pepsin, and pH on the structural integrity of the replicative intermediate (RI) dsRNA of bell pepper endornavirus (BPEV) and Cucumis melo endornavirus (CmEV), evaluated by gel electrophoresis and reverse-transcription polymerase chain reaction. Result The effect of the amylase, pepsin, and pH treatments on the dsRNA of both viruses was similar. Amylase did not appear to affect the structural integrity of the dsRNA. In contrast, gel electrophoresis analysis of pepsin-treated dsRNA samples showed an abnormal electrophoretic migration and evidence of partial dsRNA degradation. DsRNAs from both fruits were partially degraded when exposed to a pH value of 2.0 and completely degraded at a pH value of 1.0. Conclusion The results of this investigation suggest that when exposed to pepsin and pH values lower than 2.0, the RI of BPEV and CmEV lose their structural integrity. Therefore, when consuming endornavirus-infected bell pepper or melon, our digestive organs are exposed to both fragmented and full RI dsRNA of these two viruses.

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Broad and systemic immune-modulating capacity of plant-derived dsRNA

Abstract: Plant-derived endornavirus dsRNA enhances a variety of immune responses

Cited by 2 publications

References 69 publications

Viral RNA recognition by LGP2 and MDA5, and activation of signaling through step-by-step conformational changes

Viral RNA recognition by LGP2 and MDA5, and activation of signaling through step-by-step conformational changes

Effect of two digestive enzymes and pH on the dsRNA of endornaviruses of bell pepper and melon under in vitro conditions

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