Bioinformatics analysis of organizational and expressional characterizations of the IFNs, IRFs and CRFBs in grass carp Ctenopharyngodon idella

Liao, Zhiwei; Wan, Quanyuan; Su, Jian

doi:10.1016/j.dci.2016.03.020

Cited by 55 publications

(21 citation statements)

References 47 publications

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“…To identify the roles of LGP2 in GCRV-mediated IFNs and NF-κBs induction, we examined the promoter activities of all the members of grass carp IFNs (type I IFNs: IFN1, IFN2, IFN3, IFN4; type II IFNs: IFNγ1, IFNγ2) (43) and NF-κBs (NF-κB1, NF-κB2) upon LGP2 overexpression. In all these effector molecules, IFN2, IFN4, and IFNγ2 are early induced, so their promoter activities were examined at 12 h post-GCRV inoculation, and the others were investigated at 24 h. As shown in Figures 1A,B, except for IFN2, the promoter activities of all the examined genes were significantly suppressed in LGP2 overexpression cells under mock and GCRV-infected conditions.…”

Section: Resultsmentioning

confidence: 99%

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Grass Carp Laboratory of Genetics and Physiology 2 Serves As a Negative Regulator in Retinoic Acid-Inducible Gene I- and Melanoma Differentiation-Associated Gene 5-Mediated Antiviral Signaling in Resting State and Early Stage of Grass Carp Reovirus Infection

et al. 2017

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Laboratory of genetics and physiology 2 (LGP2) is a key component of RIG-I-like receptors (RLRs). However, the lack of the caspase recruitment domains (CARDs) results in its controversial functional performance as a negative or positive regulator in antiviral responses. Especially, no sufficient evidence uncovers the functional mechanisms of LGP2 in RLR signaling pathways in teleost. Here, negative regulation mechanism of LGP2 in certain situations in retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5)-mediated antiviral responses was identified in Ctenopharyngodon idella kidney cells. LGP2 overexpression inhibits synthesis and phosphorylation of interferon regulatory factor 3/7 (IRF3/7), and mRNA levels and promoter activities of IFNs and NF-κBs in resting state and early phase of grass carp reovirus (GCRV) infection. Knockdown of LGP2 obtains opposite effects. Luciferase report assay indicates that LGP2 works at the upstream of RIG-I and MDA5. LGP2 binds to RIG-I and MDA5 with diverse domain preference and which is independent of GCRV infection. Furthermore, LGP2 restrains K63-linked ubiquitination of RIG-I and MDA5 in various degrees. These differences result in disparate repressive mechanisms of LGP2 to RIG-I- and MDA5-mediated signal activations of IFN-β promoter stimulator 1 and mediator of IRF3 activation. Interestingly, LGP2 also inhibits K48-linked RIG-I and MDA5 ubiquitination to suppress proteins degradation, which guarantees the basal protein levels for subsequently rapid signal activation. All these results reveal a mechanism that LGP2 functions as a suppressor in RLR signaling pathways to maintain cellular homeostasis in resting state and early phase during GCRV infection.

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Section: Resultsmentioning

confidence: 99%

“…LGP2 can inhibit antiviral signaling independent of dsRNA or virus infection (15). IRF family has been demonstrated to contain 9 members in mammals, 10 members in avian, and 13 members in fish (43). IRF3 and IRF7, two structurally homologous members, are able to activate fish IFN promoters and upregulate fish IFNs and ISGs (52).…”

Section: Discussionmentioning

confidence: 99%

Grass Carp Laboratory of Genetics and Physiology 2 Serves As a Negative Regulator in Retinoic Acid-Inducible Gene I- and Melanoma Differentiation-Associated Gene 5-Mediated Antiviral Signaling in Resting State and Early Stage of Grass Carp Reovirus Infection

et al. 2017

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“…Some, if not all of these, subgroups exist in primitive teleosts and may have been lost in certain teleost lineages during evolution. For instance, only three of the subgroups, IFNa, c, and d are present in cyprinids, such as zebrafish and carps (11, 40–42). However, the IFNh subgroup identified here cannot be assigned to any subgroups found in salmonids and cyprinids and, hence, represents a novel phylogenetic group.…”

Section: Discussionmentioning

confidence: 99%

Identification of Two Subgroups of Type I IFNs in Perciforme Fish Large Yellow Croaker Larimichthys crocea Provides Novel Insights into Function and Regulation of Fish Type I IFNs

Ding

Huang

et al. 2016

Front. Immunol.

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Like mammals, fish possess an interferon regulatory factor (IRF) 3/IRF7-dependent type I IFN responses, but the exact mechanism by which IRF3/IRF7 regulate the type I IFNs remains largely unknown. In this study, we identified two type I IFNs in the Perciforme fish large yellow croaker Larimichthys crocea, one of which belongs to the fish IFNd subgroup and the other is assigned to a novel subgroup of group I IFNs in fish, tentatively termed IFNh. The two IFN genes are constitutively expressed in all examined tissues, but with varied expression levels. Both IFN genes can be rapidly induced in head kidney and spleen tissues by polyinosinic–polycytidylic acid. The recombinant IFNh was shown to be more potent to trigger a rapid induction of the antiviral genes MxA and protein kinase R than the IFNd, suggesting that they may play distinct roles in regulating early antiviral immunity. Strikingly, IFNd, but not IFNh, could induce the gene expression of itself and IFNh through a positive feedback loop mediated by the IFNd-dependent activation of IRF3 and IRF7. Furthermore, our data demonstrate that the induction of IFNd can be enhanced by the dimeric formation of IRF3 and IRF7, while the IFNh expression mainly involves IRF3. Taken together, our findings demonstrate that the IFN responses are diverse in fish and are likely to be regulated by distinct mechanisms.

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“…The contributions of IRF1/3/7 to the induction of IFNφ1 and IFNφ3 have been studied in vitro, providing first insights for anatomical complementarity of different IFN [35], as detailed below. In grass carp ( Ctenopharyngodon idella ), four type I IFN were also identified, CiIFN1 and four with two cysteines (group I) and CiIFN2 and three with four cysteines (group II); group II IFNs were transiently induced in gills and spleen by GCRV infection in adult fish, while CiIFN1 was constitutively expressed in gills, spleen, liver and gut, and CiIFN4 was never detectable in any condition tested [36]. …”

Section: Differential Expression and Functional Properties Of Fishmentioning

confidence: 99%

The Peculiar Characteristics of Fish Type I Interferons

Boudinot

Langevin

Secombes

et al. 2016

Viruses

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Antiviral type I interferons (IFNs) have been discovered in fish. Genomic studies revealed their considerable number in many species; some genes encode secreted and non-secreted isoforms. Based on cysteine motifs, fish type I IFNs fall in two subgroups, which use two different receptors. Mammalian type I IFN genes are intronless while type III have introns; in fish, all have introns, but structurally, both subgroups belong to type I. Type I IFNs likely appeared early in vertebrates as intron containing genes, and evolved in parallel in tetrapods and fishes. The diversity of their repertoires in fish and mammals is likely a convergent feature, selected as a response to the variety of viral strategies. Several alternative nomenclatures have been established for different taxonomic fish groups, calling for a unified system. The specific functions of each type I gene remains poorly understood, as well as their interactions in antiviral responses. However, distinct induction pathways, kinetics of response, and tissue specificity indicate that fish type I likely are highly specialized, especially in groups where they are numerous such as salmonids or cyprinids. Unravelling their functional integration constitutes the next challenge to understand how these cytokines evolved to orchestrate antiviral innate immunity in vertebrates.

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Bioinformatics analysis of organizational and expressional characterizations of the IFNs, IRFs and CRFBs in grass carp Ctenopharyngodon idella

Cited by 55 publications

References 47 publications

Grass Carp Laboratory of Genetics and Physiology 2 Serves As a Negative Regulator in Retinoic Acid-Inducible Gene I- and Melanoma Differentiation-Associated Gene 5-Mediated Antiviral Signaling in Resting State and Early Stage of Grass Carp Reovirus Infection

Grass Carp Laboratory of Genetics and Physiology 2 Serves As a Negative Regulator in Retinoic Acid-Inducible Gene I- and Melanoma Differentiation-Associated Gene 5-Mediated Antiviral Signaling in Resting State and Early Stage of Grass Carp Reovirus Infection

Identification of Two Subgroups of Type I IFNs in Perciforme Fish Large Yellow Croaker Larimichthys crocea Provides Novel Insights into Function and Regulation of Fish Type I IFNs

The Peculiar Characteristics of Fish Type I Interferons

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