The cytosolic sensor, DDX41, activates antiviral and inflammatory immunity in response to stimulation with double-stranded DNA adherent cells of the olive flounder, Paralichthys olivaceus

Quynh, Nhu Truong; Hikima, Jun-ichi; Kim, Youngrim; Fagutao, Fernand F.; Kim, Mee Sun; Aoki, Takashi; Jung, Taehun

doi:10.1016/j.fsi.2015.03.008

Cited by 38 publications

(22 citation statements)

References 26 publications

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“…Although DDX41 belongs to the same superfamily of helicases as Dicer and RLRs (Singleton et al, 2007), it is a DEAD-box helicase rather than a DRA (Luo et al, 2013), and diverged from DRAs more than 1500 mya ( Figure 6E). DDX41 was previously known to be involved in splicing, translation and many other cellular RNA processes (Jiang et al, 2017;Peters et al, 2017;Polprasert et al, 2015), but was recently shown to participate in foreign DNA sensing, albeit through a poorly understood mechanism (Parvatiyar et al, 2012;Quynh et al, 2015;Zhang et al, 2011). DDX41 does not contain a Hel2i domain, but harbors Hel1 and Hel2 that share the RecA-like fold (Omura et al, 2016).…”

Section: Distinct Trim Proteins Recognize Common Epitopes In Diverse mentioning

confidence: 99%

Structural analysis of RIG-I-like receptors reveals ancient rules of engagement between diverse RNA helicases and TRIM ubiquitin ligases

Kato

Ahmad

Zhu

et al. 2020

Preprint

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RNA helicases and ubiquitin E3 ligases mediate many critical functions within cells, but their actions have been studied largely in distinct biological contexts. Here, we uncover evolutionarily conserved rules of engagement between RNA helicases and tripartite motif (TRIM) E3 ligases that lead to their functional coordination in vertebrate innate immunity. Using cryo-electron microscopy and biochemistry, we show that RIG-I-like receptors (RLRs), viral RNA receptors with helicase domains, interact with their cognate TRIM/TRIM-like E3 ligases through similar epitopes in the helicase domains. Their interactions are avidity-driven, restricting the actions of TRIM/TRIM-like proteins and consequent immune activation to RLR multimers. Mass-spectrometry and phylogeny-guided biochemical analyses further reveal that similar rules of engagement apply to diverse RNA helicases and TRIM/TRIM-like proteins. Our analyses thus reveal not only conserved substrates for TRIM proteins but also unexpectedly deep evolutionary connections between TRIM proteins and RNA helicases, thereby linking ubiquitin and RNA biology throughout animal evolution.

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Section: Distinct Trim Proteins Recognize Common Epitopes In Diverse mentioning

confidence: 99%

Structural analysis of RIG-I-like receptors reveals ancient rules of engagement between diverse RNA helicases and TRIM ubiquitin ligases

Kato

Ahmad

Zhu

et al. 2020

Preprint

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“…Earlier studies have reported significantly enhanced expression of DDX41 in adherent (monocyte-like) cells after stimulation with a DNA virus, implying a role in sensing cytosolic double-stranded DNA (dsDNA). In addition, DDX41 overexpression induced antiviral and inflammatory cytokine gene expression after c-di-GMP treatment (Quynh et al, 2015). In view of the ability of DDX41 to stimulate the IFN-mediated immune response, here we showed the adjuvant effect of DDX41 which can be used in conjunction with fish DNA vaccines.…”

Section: Resultsmentioning

confidence: 72%

“…The cDNA samples generated were diluted 10 times with RNAse-free water and used as a template for RT-qPCR to evaluate the expression of several innate immune response genes, including IFN-1, IRF-3, ISG-15 and IL-1β. All primers (Table 1) employed have been reported and optimized in previous studies (Ohtani et al, 2010;Ohtani et al, 2012;Quynh et al, 2015). The specificity of amplification was verified based on analysis of dissociation curves.…”

Section: Analysis Of Ifn-related Genesmentioning

confidence: 99%

“…DDX41 from olive flounder functions in a similar manner as its mammalian counterpart, wherein its expression triggers activation of the IFN-mediated response. The fulllength olive flounder DDX41 gene is 2267 bp long and encodes 614 putative amino acids, including the functional domains, DEAD box and helicase (Quynh et al, 2015). In Quynh et al's work, over expression of DDX41 in HINAE cells (flounder embryonic cells) stimulated via introduction of C-di-GMP (used as a CDN representative) enhanced the transcriptional activity of the IFN-1 promoter.…”

Section: Introductionmentioning

confidence: 99%

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Immunostimulatory effect of DDX41 of olive flounder (Paralichthys olivaceus)

Lazarte

Kim

Lee

et al. 2017

Food and Agricultural Immunology

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The cellular DEAD-box helicase DDX41, which functions as an initial sensor for cytoplasmic DNA, is involved in the activation of type I interferon (IFN-1) immune response in olive flounder. A plasmid encoding DDX41 (pEF-D) was introduced into flounder cells in vitro and in vivo. Immune responses induced by DDX41 were evaluated by relative quantification value (ΔΔCt) method of RT-qPCR using specific IFN-related gene primers. Results in in vitro, transcript levels of IFN-1, IRF-3, ISG-15 and IL-1β were significantly higher in pEF-D-than pEF-A-transfected cells, with 15-, 4-, 10-and 32-fold changes, respectively. In vivo, elevated expression of these genes was observed in the kidney of pEF-D group on days 1 and 3 post-treatment. The viral challenge test revealed higher survival rate in fish treated with pEF-D (67.5%) than controls, PBS-and pEF-A-treated fish (45%). Conclusively DDX41 elicits a robust IFNmediated immune response, validating its adjuvant property. ARTICLE HISTORY

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“…Compared to mammals, the role of non-RLR DExD/H-box RNA helicases in antiviral response of fish is poorly described. The expression of fish non-RLR DExD/H-box RNA helicases in response to DNA and RNA viruses, poly(I:C) stimulation as well as to bacterial infection and CpG was studied in different fish species [ 100 , 103 , 104 , 105 , 106 , 107 ]. The results of these studies are summarized in Table 1 .…”

Section: Non-rlr Dexd/h-box Rna Helicasesmentioning

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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The cytosolic sensor, DDX41, activates antiviral and inflammatory immunity in response to stimulation with double-stranded DNA adherent cells of the olive flounder, Paralichthys olivaceus

Cited by 38 publications

References 26 publications

Structural analysis of RIG-I-like receptors reveals ancient rules of engagement between diverse RNA helicases and TRIM ubiquitin ligases

Structural analysis of RIG-I-like receptors reveals ancient rules of engagement between diverse RNA helicases and TRIM ubiquitin ligases

Immunostimulatory effect of DDX41 of olive flounder (Paralichthys olivaceus)

Cytosolic Sensors for Pathogenic Viral and Bacterial Nucleic Acids in Fish

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