Interferons lambda, new cytokines with antiviral activity

Lopušná, Katarína; Režuchová, Ingeborg; Betáková, Tatiana; Skovranová, L; Tomaskova, Jana; Lukáčiková, Ľubomíra; Kabát, Peter

doi:10.4149/av_2013_02_171

Cited by 47 publications

(36 citation statements)

References 50 publications

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“…These cytokines are mainly produced by blood cells, lymphoid tissues, and epithelial cells. For example, interferons (IFNs), which are anti-viral cytokines produced by lymphocytes and epithelial cells, are dramatically induced by various viral infections such as influenza (Qin et al, 2011b; Högner et al, 2013; Lopušná et al, 2013). This induction may contribute to the elimination of viruses in vivo .…”

Section: Introductionmentioning

confidence: 99%

Cytokine production and signaling pathways in respiratory virus infection

Kimura¹,

Yoshizumi²,

Ishii³

et al. 2013

Front. Microbiol.

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Section: Introductionmentioning

confidence: 99%

Cytokine production and signaling pathways in respiratory virus infection

Kimura¹,

Yoshizumi²,

Ishii³

et al. 2013

Front. Microbiol.

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“…Using qPCR and ELISA as well as additional subjects, we further confirmed at the transcription level and protein level that IFN-α and IL-29 were indeed significantly decreased in ADEH+ as compared to ADEH− and normal controls (Fig 2 & Fig 3). Since type I and type III IFNs signaling are the hallmarks for antiviral innate immune responses, 32–33 these data demonstrate that innate immune responses are impaired in ADEH+ subjects. All ADEH+ subjects were serological positive of anti-HSV-1 IgG (Supplemental Table I), indicating that ADEH+ patients are capable to establish specific adaptive immune response to HSV-1 infection.…”

Section: Discussionmentioning

confidence: 87%

Identification of novel gene signatures in patients with atopic dermatitis complicated by eczema herpeticum

Bin

Edwards

Heiser

et al. 2014

Journal of Allergy and Clinical Immunology

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Background A subset of patients with atopic dermatitis (AD) is prone to disseminated herpes simplex virus (HSV) infection, i.e. eczema herpeticum (ADEH+). Biomarkers that identify ADEH+ are lacking. Objective To search for novel ADEH+ gene signatures in peripheral blood mononuclear cells (PBMCs). Methods A RNA-sequencing (RNA-seq) approach was applied to evaluate global transcriptional changes using PBMCs from ADEH+ and AD without a history of EH (ADEH−). Candidate genes were confirmed by qPCR or ELISA. RESULTS ADEH+ PBMCs had distinct changes to the transcriptome when compared to ADEH− PBMCs following HSV-1 stimulation: 792 genes were differentially expressed at a false discovery rate (FDR) < 0.05 (ANOVA), and 15 type I and type III interferon (IFN) genes were among the top 20 most down-regulated genes in ADEH+. We further validated that IFN-α and IL-29 mRNA and protein levels were significantly decreased in HSV-1 stimulated PBMCs from ADEH+ compared to ADEH− and normal. Ingenuity pathway analysis (IPA) demonstrated that the up-stream regulators of type I and type III IFNs, IRF3 and IRF7, was significantly inhibited in ADEH+ based on the down-regulation of their target genes. Furthermore, we found that gene expression of IRF3 and IRF7 were significantly decreased in HSV-1 stimulated PBMC from ADEH+ subjects. CONCLUSIONS PBMCs from ADEH+ have a distinct immune response following HSV-1 exposure compared to ADEH−. Inhibition of the IRF3 and IRF7 innate immune pathways in ADEH+ may be important mechanism for increased susceptibility to disseminated viral infection.

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“…They share with type I IFNs not only functional similarity, including the ability to induce an antiviral state in cells, but also expression patterns, trigger common signal transduction cascades and sets of stimulated genes (Onoguchi et al, 2007). The IFN-λ subfamily (classified as type III IFN) contains four cytokines (IFN-λ1, IFN-λ2, and IFN-λ3; first designed as interleukin-29 (IL-29, IL-28A, and IL-28B) (reviewed by Lopušná et al, 2013). Recently, fourth family member, IFN-λ4, was described.…”

Section: Introductionmentioning

confidence: 99%

Interferon lambda induces antiviral response to herpes simplex virus 1 infection

Lopušná¹,

Režuchová²,

Kabát³

et al. 2014

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Summary. -Lambda interferons (IFN-λ) are known to induce potent antiviral response in a wide variety of target cells. They activate the same intracellular signalling pathways and have similar biological activities as IFN-α/β, including antiviral activity, but signal via distinct receptor complex, which is expressed in a celland species-specific manner. IFN-λ was reported to induce in vitro marked antiviral activity against various RNA viruses, but corresponding data on DNA viruses are sparse. Therefore we examined the IFN-λ1 induced antiviral activity against two strains of herpes simplex virus 1, a highly pathogenic ANGpath and moderately pathogenic KOS. The antiviral response was determined in vitro in Vero cells, known as deficient in production of type I IFNs and in Vero E6 cells, responding to viral infection with abundant IFN-λ production, although deficient in production of type I IFNs. The results showed that IFN-λ1 induced in Vero cells higher antiviral activity against ANGpath strain than against KOS strain. In Vero E6 cells endogenous IFN-λ induced higher antiviral activity against ANGpath strain than against KOS strain, but because of the virus induction of IFN-λ expression the antiviral activity was detected later. The observed differences between the IFN-λ1-induced antiviral activities against viral strains of various pathogenicity suggest that virus attributes may play role in the antiviral state of cells induced by IFN-λ.

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Interferons lambda, new cytokines with antiviral activity

Cited by 47 publications

References 50 publications

Cytokine production and signaling pathways in respiratory virus infection

Cytokine production and signaling pathways in respiratory virus infection

Identification of novel gene signatures in patients with atopic dermatitis complicated by eczema herpeticum

Interferon lambda induces antiviral response to herpes simplex virus 1 infection

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