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NOD1 Promotes Antiviral Signaling by Binding Viral RNA and Regulating the Interaction of MDA5 and MAVS
Wu, Xiao Man1,2; Zhang, Jie1; Li, Peng Wei1,2; Hu, Yi Wei1,2; Cao, Lu1,2; Ouyang, Songying3,4; Bi, Yong Hong1; Nie, Pin1,2,5; Chang, Ming Xian1,2,5,6
2020-04-15
Source PublicationJOURNAL OF IMMUNOLOGY
ISSN0022-1767
Volume204Issue:8Pages:2216-2231
Abstract

Nucleotide oligomerization domain-like receptors (NLRs) and RIG-I-like receptors (RLRs) detect diverse pathogen-associated molecular patterns to activate the innate immune response. The role of mammalian NLR NOD1 in sensing bacteria is well established. Although several studies suggest NOD1 also plays a role in sensing viruses, the mechanisms behind this are still largely unknown. In this study, we report on the synergism and antagonism between NOD1 and MDA5 isoforms in teleost. In zebrafish, the overexpression of NOD1 enhances the antiviral response and mRNA abundances of key antiviral genes involved in RLR-mediated signaling, whereas the loss of NOD1 has the opposite effect. Notably, spring viremia of carp virus-infected NOD1(-/-) zebrafish exhibit reduced survival compared with wild-type counterparts. Mechanistically, NOD1 targets MDA5 isoforms and TRAF3 to modulate the formation of MDA5-MAVS and TRAF3-MAVS complexes. The cumulative effects of NOD1 and MDA5a (MDA5 normal form) were observed for the binding with poly(I:C) and the formation of the MDA5a-MAVS complex, which led to increased transcription of type I IFNs and ISGs. However, the antagonism between NOD1 and MDA5b (MDA5 truncated form) was clearly observed during proteasomal degradation of NOD1 by MDA5b. In humans, the interactions between NOD1-MDA5 and NOD1-TRAF3 were confirmed. Furthermore, the roles that NOD1 plays in enhancing the binding of MDA5 to MAVS and poly(I:C) are also evolutionarily conserved across species. Taken together, our findings suggest that mutual regulation between NOD1 and MDA5 isoforms may play a crucial role in the innate immune response and that NOD1 acts as a positive regulator of MDA5/MAVS normal form-mediated immune signaling in vertebrates.

DOI10.4049/jimmunol.1900667
Indexed BySCI
Language英语
WOS Research AreaImmunology
WOS SubjectImmunology
WOS IDWOS:000525420100019
WOS KeywordRIG-I ; BACTERIAL-INFECTION ; IMMUNE ; OLIGOMERIZATION ; DOMAIN ; INTERFERON ; EXPRESSION ; RECEPTORS ; ACTIVATION ; RESPONSES
PublisherAMER ASSOC IMMUNOLOGISTS
Citation statistics
Cited Times:3[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/36046
Collection鱼类生物学及渔业生物技术研究中心_期刊论文
Corresponding AuthorChang, Ming Xian
Affiliation1.Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Hubei, Peoples R China
2.Univ Chinese Acad Sci, Beijing 10049, Peoples R China
3.Fujian Normal Univ, Coll Life Sci, Biomed Res Ctr South China, Key Lab Innate Immune Biol Fujian Prov, Fuzhou 350117, Peoples R China
4.Fujian Normal Univ, Coll Life Sci, Key Lab OptoElect Sci & Technol Med, Minist Educ, Fuzhou 350117, Peoples R China
5.Minist Agr, LiKey Lab Aquaculture Dis Control, Wuhan 430072, Hubei, Peoples R China
6.Chinese Acad Sci, Innovat Acad Seed Design, Wuhan 430072, Peoples R China
Recommended Citation
GB/T 7714
Wu, Xiao Man,Zhang, Jie,Li, Peng Wei,et al. NOD1 Promotes Antiviral Signaling by Binding Viral RNA and Regulating the Interaction of MDA5 and MAVS[J]. JOURNAL OF IMMUNOLOGY,2020,204(8):2216-2231.
APA Wu, Xiao Man.,Zhang, Jie.,Li, Peng Wei.,Hu, Yi Wei.,Cao, Lu.,...&Chang, Ming Xian.(2020).NOD1 Promotes Antiviral Signaling by Binding Viral RNA and Regulating the Interaction of MDA5 and MAVS.JOURNAL OF IMMUNOLOGY,204(8),2216-2231.
MLA Wu, Xiao Man,et al."NOD1 Promotes Antiviral Signaling by Binding Viral RNA and Regulating the Interaction of MDA5 and MAVS".JOURNAL OF IMMUNOLOGY 204.8(2020):2216-2231.
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