Dataset Information

Functional characterization of canine interferon-lambda.

ABSTRACT: In this study, we provide the first comprehensive annotation of canine interferon-? (CaIFN-?, type III IFN). Phylogenetic analysis based on genomic sequences indicated that CaIFN-? is located in the same branch with Swine IFN-?1 (SwIFN-?), Bat IFN-?1 (BaIFN-?), and human IFN-?1 (HuIFN-?1). CaIFN-? was cloned, expressed in Escherichia coli, and purified to further investigate the biological activity in vitro. The recombinant CaIFN-? (rCaIFN-?) displayed potent antiviral activity on both homologous and heterologous animal cells in terms of inhibiting the replication of the New Jersey serotype of vesicular stomatitis virus (VSV), canine parvovirus, and influenza virus A/WSN/33 (H1N1), respectively. In addition, we also found that rCaIFN-? exhibits a significant antiproliferative response against A72 canine tumor cells and MDCK cells in a dose-dependent manner. Furthermore, CaIFN-? activated the JAK-STAT signaling pathway. To evaluate the expression of CaIFN-? induced by virus and the expression of IFN-stimulated genes (ISGs) induced by rCaIFN-? in the MDCK cells, we measured the relative mRNA level of CaIFN-? and ISGs (ISG15, Mx1, and 2'5'-OAS) by quantitative real-time PCR and found that the mRNA level of CaIFN-? and the ISGs significantly increased after treating the MDCK cells with viruses and rCaIFN-? protein, respectively. Finally, to evaluate the binding activity of rCaIFN-? to its receptor, we expressed the extracellular domain of the canine IFN-? receptor 1 (CaIFN-?R1-EC) and determined the binding activity via ELISA. Our results demonstrated that rCaIFN-? bound tightly to recombinant CaIFN-?R1-EC (rCaIFN-?R1-EC).

SUBMITTER: Fan W

PROVIDER: S-EPMC4217014 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Functional characterization of canine interferon-lambda.

Fan Wenhui W Xu Lei L Ren Liqian L Qu Hongren H Li Jing J Liang Jingjing J Liu Wenjun W Yang Limin L Luo Tingrong T

Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 20140620 11

In this study, we provide the first comprehensive annotation of canine interferon-λ (CaIFN-λ, type III IFN). Phylogenetic analysis based on genomic sequences indicated that CaIFN-λ is located in the same branch with Swine IFN-λ1 (SwIFN-λ), Bat IFN-λ1 (BaIFN-λ), and human IFN-λ1 (HuIFN-λ1). CaIFN-λ was cloned, expressed in Escherichia coli, and purified to further investigate the biological activity in vitro. The recombinant CaIFN-λ (rCaIFN-λ) displayed potent antiviral activity on both homologou ...[more]

PMID: 24950142

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Project description:Interferon lambdas (IFN-λs; IFNL1-4) modulate immunity in the context of infections and autoimmune diseases, through a network of induced genes. IFN-λs act by binding to the heterodimeric IFN-λ receptor (IFNLR), activating a STAT phosphorylation-dependent signaling cascade. Thereby hundreds of IFN-stimulated genes are induced, which modulate various immune functions via complex forward and feedback loops. When compared to the well-characterized IFN-α signaling cascade, three important differences have been discovered. First, the IFNLR is not ubiquitously expressed: in particular, immune cells show significant variation in the expression levels of and susceptibilities to IFN-λs. Second, the binding affinities of individual IFN-λs to the IFNLR varies greatly and are generally lower compared to the binding affinities of IFN-α to its receptor. Finally, genetic variation in the form of a series of single-nucleotide polymorphisms (SNPs) linked to genes involved in the IFN-λ signaling cascade has been described and associated with the clinical course and treatment outcomes of hepatitis B and C virus infection. The clinical impact of IFN-λ signaling and the SNP variations may, however, reach far beyond viral hepatitis. Recent publications show important roles for IFN-λs in a broad range of viral infections such as human T-cell leukemia type-1 virus, rotaviruses, and influenza virus. IFN-λ also potentially modulates the course of bacterial colonization and infections as shown for Staphylococcus aureus and Mycobacterium tuberculosis. Although the immunological processes involved in controlling viral and bacterial infections are distinct, IFN-λs may interfere at various levels: as an innate immune cytokine with direct antiviral effects; or as a modulator of IFN-α-induced signaling via the suppressor of cytokine signaling 1 and the ubiquitin-specific peptidase 18 inhibitory feedback loops. In addition, the modulation of adaptive immune functions via macrophage and dendritic cell polarization, and subsequent priming, activation, and proliferation of pathogen-specific T- and B-cells may also be important elements associated with infectious disease outcomes. This review summarizes the emerging details of the IFN-λ immunobiology in the context of the host immune response and viral and bacterial infections.

Dataset Information

Functional characterization of canine interferon-lambda.

Publications

Functional characterization of canine interferon-lambda.

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