A DN-mda5 transgenic zebrafish model demonstrates that Mda5 plays an important role in snakehead rhabdovirus resistance

Gabor, Kristin A.; Charette, Jeremy R.; Pietraszewski, Matthew; Wingfield, D.J.; Shim, Juyoung; Millard, Paul J.; Kim, Carol H.

doi:10.1016/j.dci.2015.01.006

Cited by 14 publications

(13 citation statements)

References 62 publications

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“…Subsequently, two splicing forms of MDA5, MDA5a and MDA5b, were identified in zebrafish, and activation of type I IFN promoters and immune defence against SVCV infection were found in EPC cells transfected with plasmids overexpressing the two isoforms . It is further confirmed in other studies that zebrafish MDA5 can increase the expression of type I IFNs in embryos and induce IFN promoter activities . Moreover, the overexpression of zebrafish MDA5 in ZFL cells can provide resistance against snakehead rhabdovirus infection.…”

Section: Antiviral and Antibacterial Functions Of Rlrs In Teleost Fishsupporting

confidence: 53%

“…Moreover, the overexpression of zebrafish MDA5 in ZFL cells can provide resistance against snakehead rhabdovirus infection. The role of MDA5 is more clearly revealed through the establishment of dominant‐negative MDA5 gene (CARD deletion) transgenic zebrafish, in which higher mortality rate and virus titre were observed after snakehead rhabdovirus infection . In addition, a recent report showed that IFN and IFN‐stimulated response element (ISRE) promoters were activated in cells overexpressing grouper MDA5, leading to the induction of IRF3, IRF7 and tumour necrosis factor receptor‐associated factor 6 (TRAF6) and the expression of pro‐inflammatory cytokines, but the transcriptional level of viral genes was significantly reduced including MCP, Vp19 from Singapore grouper iridovirus, and CP and RdRp from red‐spotted grouper nervous necrosis virus …”

Section: Antiviral and Antibacterial Functions Of Rlrs In Teleost Fishmentioning

confidence: 99%

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Retinoic acid‐inducible gene I (RIG‐I)‐like receptors (RLRs) in fish: current knowledge and future perspectives

2017

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Summary Retinoic acid‐inducible gene I (RIG‐I) ‐like receptors (RLRs) are found conservatively present in teleost fish. All three members, RIG‐I, MDA5 and LGP2, together with the downstream molecules such as MITA, TRAF3 and TBK1, have been identified in a range of fish species. However, it is unexpected that RIG‐I has not been reported in fish of Acanthopterygii, and it would be important to clarify the presence and role of the RIG‐I gene in a broad range of taxa in Teleostei. RLRs in fish can be induced in vivo and in vitro by viral pathogens as well as synthetic dsRNA, poly(I:C), leading to the production of type I interferons (IFNs) and the expression of IFN‐stimulated genes (ISGs). Bacterial pathogens, such as Edwardsiella tarda, and their components, such as lipopolysaccharide are also found to induce the expression of RLRs, and whether such induction was mediated through the direct recognition by RLRs or through crosstalk with other pattern recognition receptors recognizing directly bacterial pathogen‐associated molecular patterns awaits to be investigated. On the other hand, RLR‐activated type I IFN production can be negatively regulated in fish by molecules, such as TBK‐1‐like protein and IRF10, which are found to negatively regulate RIG‐I and MAVS‐activated type I IFN production, and to block MITA or bind ISRE motifs, respectively. It is considered that the evolutionary occurrence of RLRs in fish, and their recognized ligands, especially those from their fish pathogens, as well as the mechanisms involved in the RLR signalling pathways, are of significant interest for further investigation.

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Section: Antiviral and Antibacterial Functions Of Rlrs In Teleost Fishsupporting

confidence: 53%

Section: Antiviral and Antibacterial Functions Of Rlrs In Teleost Fishmentioning

confidence: 99%

Retinoic acid‐inducible gene I (RIG‐I)‐like receptors (RLRs) in fish: current knowledge and future perspectives

2017

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“…Zebrafish MDA5 has a conserved DExD/H domain and a helix C domain but lacks an N-terminal CARD domain, which may not be directly involved in downstream signaling. Recently, Gabor et al 85 reported the role of zebrafish MDA5 in protection against snakehead rhabdovirus infection, suggesting the conservation of this antiviral signaling pathway in lower vertebrates and the possession of recognition strategies for a wide array of viruses by fish early in evolution.…”

Section: Pattern Recognition Receptorsmentioning

confidence: 99%

Pattern recognition receptors in zebrafish provide functional and evolutionary insight into innate immune signaling pathways

et al. 2016

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Pattern recognition receptors (PRRs) and their signaling pathways have essential roles in recognizing various components of pathogens as well as damaged cells and triggering inflammatory responses that eliminate invading microorganisms and damaged cells. The zebrafish relies heavily on these primary defense mechanisms against pathogens. Here, we review the major PRR signaling pathways in the zebrafish innate immune system and compare these signaling pathways in zebrafish and humans to reveal their evolutionary relationship and better understand their innate immune defense mechanisms.

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“…Zebrafish dominant-negative mda5 mutants lacking CARD domains were more susceptible to snakehead rhabdovirus (SHRV) infection and showed reduced ifnφ1 up-regulation during SHRV infection as compared to wild-type larvae. This effect was rescued by overexpression of mda5 [ 113 ]. Functional blockade of mda5 in the EPC cells, by using dominant negative mutants of MDA5 (MDA5-DN), significantly attenuated in fish activation of IFN promoters and up-regulation of IFNs and ISGs during SVCV infection [ 109 ].…”

Section: Rlrs In Fishmentioning

confidence: 99%

“…The overexpression of zebrafish mda5a and mda5b induced strong activation of type I IFN promoter in EPC cells with mda5a exhibiting stronger induction [ 92 ]. The protective effect of mda5 overexpression against viral infection was demonstrated by reduced cytopathic effect (CPE) in zebrafish liver cells (ZFL) upon SHRV infection and EPC cells upon SVCV or GCRV infection [ 79 , 113 ]. Other studies indicated that overexpression of orange-spotted grouper mda5 in Grouper spleen (GS) cells delayed the CPE progression during Singapore grouper iridovirus (SGIV) or red spotted grouper nervous necrosis virus (RGNNV) infection [ 88 ].…”

Section: Rlrs In Fishmentioning

confidence: 99%

Cytosolic Sensors for Pathogenic Viral and Bacterial Nucleic Acids in Fish

Mojzesz

Rakus

Chadzińska

et al. 2020

IJMS

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Recognition of the non-self signature of invading pathogens is a crucial step for the initiation of the innate immune mechanisms of the host. The host response to viral and bacterial infection involves sets of pattern recognition receptors (PRRs), which bind evolutionarily conserved pathogen structures, known as pathogen-associated molecular patterns (PAMPs). Recent advances in the identification of different types of PRRs in teleost fish revealed a number of cytosolic sensors for recognition of viral and bacterial nucleic acids. These are DExD/H-box RNA helicases including a group of well-characterized retinoic acid inducible gene I (RIG-I)-like receptors (RLRs) and non-RLR DExD/H-box RNA helicases (e.g., DDX1, DDX3, DHX9, DDX21, DHX36 and DDX41) both involved in recognition of viral RNAs. Another group of PRRs includes cytosolic DNA sensors (CDSs), such as cGAS and LSm14A involved in recognition of viral and intracellular bacterial dsDNAs. Moreover, dsRNA-sensing protein kinase R (PKR), which has a role in antiviral immune responses in higher vertebrates, has been identified in fish. Additionally, fish possess a novel PKR-like protein kinase containing Z-DNA binding domain, known as PKZ. Here, we review the current knowledge concerning cytosolic sensors for recognition of viral and bacterial nucleic acids in teleosts.

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A DN-mda5 transgenic zebrafish model demonstrates that Mda5 plays an important role in snakehead rhabdovirus resistance

Cited by 14 publications

References 62 publications

Retinoic acid‐inducible gene I (RIG‐I)‐like receptors (RLRs) in fish: current knowledge and future perspectives

Retinoic acid‐inducible gene I (RIG‐I)‐like receptors (RLRs) in fish: current knowledge and future perspectives

Pattern recognition receptors in zebrafish provide functional and evolutionary insight into innate immune signaling pathways

Cytosolic Sensors for Pathogenic Viral and Bacterial Nucleic Acids in Fish

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