The differential antiviral activities of chicken interferon α (ChIFN-α) and ChIFN-β are related to distinct interferon-stimulated gene expression.

Hongren Qu,Jing Li,Xiaojuan Jia,Yuhai Bi,Limin Yang,Lei Xu,Wenjun Liu,Shanshan Meng,Lei Sun,Annabel Valledor

doi:10.1371/journal.pone.0059307

Abstract

Chicken interferon α (ChIFN-α) and ChIFN-β are type I IFNs that are important antiviral cytokines in the innate immune system. In the present study, we identified the virus-induced expression of ChIFN-α and ChIFN-β in chicken fibroblast DF-1 cells and systematically evaluated the antiviral activities of recombinant ChIFN-α and ChIFN-β by cytopathic-effect (CPE) inhibition assays. We found that ChIFN-α exhibited stronger antiviral activity than ChIFN-β in terms of inhibiting the replication of vesicular stomatitis virus, Newcastle disease virus and avian influenza virus, respectively. To elucidate the mechanism of differential antiviral activities between the two ChIFNs, we measured the relative mRNA levels of IFN-stimulated genes (ISGs) in IFN-treated DF-1 cells by real-time PCR. ChIFN-α displayed greater induction potency than ChIFN-β on several ISGs encoding antiviral proteins and MHC-I, whereas ChIFN-α was less potent than ChIFN-β for inducing ISGs involved in signaling pathways. In conclusion, ChIFN-α and ChIFN-β presented differential induction potency on various sets of ISGs, and the stronger antiviral activity of ChIFN-α is likely attributed to the greater expression levels of downstream antiviral ISGs.

Highlights

Chicken type I interferon (IFN) was the first cytokine discovered that is induced by heat-inactivated influenza virus in the chorioallantoic membranes of chicken embryos, was named IFN for its ability to directly interfere with influenza virus replication [1], and the IFN gene was subsequently cloned from a cDNA library from chicken embryonic cells [2,3]
The two ChIFNs amino acid sequences were aligned by DNAMAN and displayed 50% identity. Their putative receptor binding sites were located according to the binding site descriptions for Chicken interferon a (ChIFN-a) and ChIFN-b from the NCBI protein database and sequence alignments between the ChIFNs and human IFN (Figure 1B)
Both ChIFN-a and ChIFN-b likely contain 20 residues that interact with IFNAR1 and 27 residues that interact with IFNAR2

Summary

Introduction

Chicken type I interferon (IFN) was the first cytokine discovered that is induced by heat-inactivated influenza virus in the chorioallantoic membranes of chicken embryos, was named IFN for its ability to directly interfere with influenza virus replication [1], and the IFN gene was subsequently cloned from a cDNA library from chicken embryonic cells [2,3]. Different type I IFNs display markedly distinct antiviral, antiproliferative and pro-apoptotic activities despite sharing the same receptors [8,9,10,11,12] This led to the question of how IFN-a and IFN-b function differentially while binding to a common receptor, and several studies focus on the binding affinity of IFNs for their receptor and the cascading effect of downstream signaling pathways [13,14,15]. The cellular effects of type I IFNs are mediated by ISGs products together with IFNs themselves

Methods

Results

Conclusion