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PMID:24950142

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Citation

Fan, W, Xu, L, Ren, L, Qu, H, Li, J, Liang, J, Liu, W, Yang, L and Luo, T' (2014) Functional Characterization of Canine Interferon-Lambda. J. Interferon Cytokine Res. '

Abstract

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 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-λ exhibits a significant antiproliferative response against A72 canine tumor cells and MDCK cells in a dose-dependent manner. Furthermore, CaIFN-λ activated the JAK-STAT signaling pathway. To evaluate the expression of CaIFN-λ induced by virus and the expression of IFN-stimulated genes (ISGs) induced by rCaIFN-λ in the MDCK cells, we measured the relative mRNA level of CaIFN-λ and ISGs (ISG15, Mx1, and 2'5'-OAS) by quantitative real-time PCR and found that the mRNA level of CaIFN-λ and the ISGs significantly increased after treating the MDCK cells with viruses and rCaIFN-λ protein, respectively. Finally, to evaluate the binding activity of rCaIFN-λ to its receptor, we expressed the extracellular domain of the canine IFN-λ receptor 1 (CaIFN-λR1-EC) and determined the binding activity via ELISA. Our results demonstrated that rCaIFN-λ bound tightly to recombinant CaIFN-λR1-EC (rCaIFN-λR1-EC).

Links

PubMed Online version:10.1089/jir.2014.0009

Keywords


Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

CANLF:F1PY54

GO:0008285: negative regulation of cell proliferation

ECO:0000314:

P

Figure 3

complete
CACAO 10225

CANLF:F1PY54

GO:0046427: positive regulation of JAK-STAT cascade

ECO:0000314:

P

Figure 4

complete
CACAO 10227

CANLF:F1PY54

involved_in

GO:0008285: negative regulation of cell population proliferation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CANLF:F1PY54

involved_in

GO:0046427: positive regulation of receptor signaling pathway via JAK-STAT

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CANLF:Q75UL5

GO:0046427: positive regulation of JAK-STAT cascade

ECO:0000314:

P

Figure 4

complete
CACAO 10258

CANLF:Q75UL5

GO:0008285: negative regulation of cell proliferation

ECO:0000314:

P

Figure 3

complete
CACAO 10259

CANLF:Q75UL5

involved_in

GO:0046427: positive regulation of receptor signaling pathway via JAK-STAT

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CANLF:Q75UL5

involved_in

GO:0008285: negative regulation of cell population proliferation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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