Chicken IFN Kappa: A Novel Cytokine with Antiviral Activities

Diwakar Santhakumar,Munir Iqbal,Muhammad Munir,Venugopal Nair

doi:10.1038/s41598-017-02951-2

Abstract

Interferons (IFNs) are essential components of the host innate immune system and define first-line of defence against pathogens. In mammals, several type I IFNs are identified, however, only limited data is available on the repertoire of IFNs in avian species. Here we report the characterization of chicken IFN-κ (chIFN-κ) near the type I IFN locus on the sex-determining Z chromosome. Genetic, evolutionary and syntenic analyses indicate that chIFN-κ is a type I IFN with conserved genetic features and promoter binding sites. chIFN-κ regulated the IFN-stimulated response element signalling pathways and activated a panel of IFN-regulated genes, antiviral mediators and transcriptional regulators. Priming of chicken primary fibroblasts and tracheal organ cultures with chIFN-κ imparted cellular protections against viral infections both in vitro and ex vivo. To determine whether chIFN-κ defines the antiviral state in developing chicken embryos, we used replication-competent retroviral RCAS vector system to generate transgenic chicken embryos that constitutively and stably expressed chIFN-κ. We could demonstrate that chIFN-κ markedly inhibited the replication of avian RNA viruses in ovo. Collectively, these results shed the light on the repertoire of IFNs in avian species and provide functional data on the interaction of the chIFN-κ with RNA viruses of poultry and public health importance.

Highlights

Interferons (IFNs) are a family of pleiotropic and functionally related cytokines that play central roles in the cellular antiviral defence, antitumor, antiproliferative and immunomodulatory activities[1,2,3]
Except for synonymous mutations, the coding DNA sequence (CDS) obtained from genomic DNA of different chicken lines was similar to the sequence available in the GenBank, reported previously by Andrew Bean’s group (CSIRO, Australia)
ChIFN-κ was encoded in the opposite orientation on the Z chromosome compared to the IFN-α and IFN-β genes and is approximately 27 Mb apart from these genes (Fig. 1SB)

Summary

Introduction

Interferons (IFNs) are a family of pleiotropic and functionally related cytokines that play central roles in the cellular antiviral defence, antitumor, antiproliferative and immunomodulatory activities[1,2,3]. There are emerging evidences on genetics and immunological differences between avian species, and that they mount evolutionary diverse innate immune responses[9] Understanding these differential host responses may provide foundations to study evolutionary and functional genomic backgrounds of virus-host interactions in class Aves especially in chickens, which are notoriously been associated with emergence of influenza viruses[19, 20]. Employing retroviral gene transfer vector system, RCAS21, we generated chIFN-κ expressing transgenic chicken embryos and demonstrated its antiviral potential in ovo These analyses provided evidences on the presence of a novel and previously uncharacterized IFN gene in aves

Methods

Results

Conclusion