Human interferon-λ3 is a potent member of the type III interferon family

Dellgren, Christoffer; Gad, Hans Henrik; Hamming, Ole J.; Melchjorsen, Jesper; Hartmann, Rune

doi:10.1038/gene.2008.87

Cited by 151 publications

(126 citation statements)

References 21 publications

(24 reference statements)

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“…Furthermore, the inhibitory effect of IFN-3 on HSV-2 was more potent than that of IFN-1 and IFN-2 ( Fig. 1A and B), which is consistent with previous publications (33,34).…”

Section: Discussionsupporting

confidence: 81%

Lambda-Interferons Inhibit Herpes Simplex Virus Type 2 Replication in Human Cervical Epithelial Cells by Activating the JAK/STAT Pathway

et al. 2017

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“…Furthermore, the inhibitory effect of IFN-3 on HSV-2 was more potent than that of IFN-1 and IFN-2 ( Fig. 1A and B), which is consistent with previous publications (33,34).…”

Section: Discussionsupporting

confidence: 81%

Lambda-Interferons Inhibit Herpes Simplex Virus Type 2 Replication in Human Cervical Epithelial Cells by Activating the JAK/STAT Pathway

et al. 2017

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“…The BamHI digested fragments were cloned in pET15b digested by NcoI (blunt ended by T4 dNA pol) and BamHI. The proteins were expressed in Escherichia coli and in vitro refolded according to Dellgren et al (25). Injections of recombinant proteins diluted in PBS containing 0.1% phenol red were performed in the caudal vein as described in Ref.…”

Section: Recombinant Ifnsmentioning

confidence: 99%

The Two Groups of Zebrafish Virus-Induced Interferons Signal via Distinct Receptors with Specific and Shared Chains

Aggad

Mazel

Boudinot

et al. 2009

The Journal of Immunology

227

246

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Because the availability of fish genomic data, the number of reported sequences for fish type II helical cytokines is rapidly growing, featuring different IFNs including virus-induced IFNs (IFNφ) and IFN-γ, and IL-10 with its related cytokines (IL-20, IL-22, and IL-26). Many candidate receptors exist for these cytokines and various authors have postulated which receptor chain would be involved in which functional receptor in fish. To date, only the receptor for zebrafish IFNφ1 has been identified functionally. Three genes encoding virus-induced IFNφs have been reported in zebrafish. In addition to these genes clustered on chromosome 3, we have identified a fourth IFNφ gene on chromosome 12. All these genes possess the intron-exon organization of mammalian λ IFNs. In the zebrafish larva, all induce the expression of reporter antiviral genes; protection in a viral challenge assay was observed for IFNφ1 and IFNφ2. Using a combination of gain- and loss-of-function experiments, we also show that all zebrafish IFNφs do not bind to the same receptor. Two subgroups of fish virus-induced IFNs have been defined based on conserved cysteines, and we find that this subdivision correlates with receptor usage. Both receptor complexes include a common short chain receptor (CRFB5) and a specific long chain receptor (CRFB1 or CRFB2).

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“…Bolen et al also concluded that, among the IFN-k family, IFN-k3 was the most potent ISG inducer 11 and corroborates another study demonstrating that IFN-k3 possesses a higher level of antiviral activity than either IFN-k1 or IFN-k2. 16 The studies also intriguingly reported on a unique kinetic profile of ISG expression in IFN-a-treated Huh7 or PHHs. 11,12 Indeed, both IFN-b and IFN-k triggered a sustained ISG response; on the other hand, IFN-a produced a kinetic profile of genes that peaked at early times of treatment and then rapidly decreased (Fig.…”

mentioning

confidence: 99%

Type I and type III interferon-induced immune response: It's a matter of kinetics and magnitude

Olagnier

Hiscott

2014

Hepatology

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See Articles on Pages 1250 and 1262 T he interferon (IFN) family of cytokines, including type I and III IFNs, represent a first line of defense that "interferes" with a vast range of viral infections.1 IFN cytokines are commonly classified into distinct families, based on their structural properties and on the receptor complex through which they signal.1 Type I IFNs, including IFN-b and -a, exert their biological activities through a heterodimeric receptor complex known as IFN-a receptor (IFNAR) that consists of IFNAR1 and IFNAR2 chains. Discovered in 2003, type III IFNs, including interleukin (IL)228A (IFN-k2), IL-28B (IFN-k3), and IL-29 (IFN-k1), are distinct from type I IFNs and act through a different receptor system that is preferentially expressed on the surface of epithelial cells, including hepatocytes.2-4 Type III IFNs bind to a heterodimeric receptor consisting of the IL-10 receptor 2 chain and the interferon k receptor 1 (IFNLR1) chain that is structurally different from the IFNAR. Recently, a new coding region upstream of IFNL3 on chromosome 19q13.13, designated as IFNL4, was identified that encodes a new member of the type III IFN family, called Signaling cascades of both type I and III IFNs converge on the activation of Janus kinase (JAK)1 and tyrosine kinase (TYK)2 kinases, leading to the subsequent phosphorylation and activation of latent signal transducer and activator of transcription (STAT) transcription factors. Phosphorylated STAT1 and STAT2 heterodimerize and interact with IFN regulatory factor 9 (IRF9) to form an IFN-stimulated gene factor 3 (ISGF3) transcription complex that binds to the IFNstimulated response element (ISRE); STAT1 can also homodimerize and bind the gamma-activated sequences (GAS) element. Altogether, binding of these STAT complexes to specific promoter sequences leads to the establishment of an antiviral response through upregulation of hundreds of IFN-stimulated genes (ISGs; Fig. 1), many of which are poorly understood biologically with regard to their antiviral activity. 6 Despite what appear to be common signaling cascades, type I and III IFNs have begun to reveal divergent biological activities.7-10 However, it is still unclear whether these related cytokine family members induce common or distinct patterns of ISGs that result in the programming of divergent antiviral and/or immune modulatory states. In this issue of HEPATOLOGY, Bolen et al. and Jilg et al. have approached this question using time-resolved, microarray-based gene expression profiling in human hepatocytes. Both studies reach a similar, but somewhat unpredicted, conclusion that type I and III IFNs stimulate similar sets of ISGs, albeit with very distinct kinetics of response and magnitude of stimulation. 11,12These two parallel studies from Bolen et al. and Jilg et al. converge on an answer that contrasts with studies demonstrating that type I and III IFNs induce both overlapping and distinct sets of genes. 8,13,14 In the current experiments, transcriptome analysis from human hepatoma Huh7 cells or pri...

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Human interferon-λ3 is a potent member of the type III interferon family

Cited by 151 publications

References 21 publications

Lambda-Interferons Inhibit Herpes Simplex Virus Type 2 Replication in Human Cervical Epithelial Cells by Activating the JAK/STAT Pathway

Lambda-Interferons Inhibit Herpes Simplex Virus Type 2 Replication in Human Cervical Epithelial Cells by Activating the JAK/STAT Pathway

The Two Groups of Zebrafish Virus-Induced Interferons Signal via Distinct Receptors with Specific and Shared Chains

Type I and type III interferon-induced immune response: It's a matter of kinetics and magnitude

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