Dynamic Expression of Interferon Lambda Regulated Genes in Primary Fibroblasts and Immune Organs of the Chicken.

Mehboob Arslan,Xin Yang,Muhammad Munir,Xingjian Liu,Xiaoyuan Hu,Yinü Li,Zhifang Zhang,Diwakar Santhakumar

doi:10.3390/genes10020145

Abstract

Interferons (IFNs) are pleiotropic cytokines that establish a first line of defense against viral infections in vertebrates. Several types of IFN have been identified; however, limited information is available in poultry, especially using live animal experimental models. IFN-lambda (IFN-λ) has recently been shown to exert a significant antiviral impact against viral pathogens in mammals. In order to investigate the in vivo potential of chicken IFN-λ (chIFN-λ) as a regulator of innate immunity, and potential antiviral therapeutics, we profiled the transcriptome of chIFN-λ-stimulated chicken immune organs (in vivo) and compared it with primary chicken embryo fibroblasts (in vitro). Employing the baculovirus expression vector system (BEVS), recombinant chIFN-λ3 (rchIFN-λ3) was produced and its biological activities were demonstrated. The rchIFNλ3 induced a great array of IFN-regulated genes in primary chicken fibroblast cells. The transcriptional profiling using RNA-seq and subsequent bioinformatics analysis (gene ontology, differential expressed genes, and KEGGs analysis) of the bursa of Fabricious and the thymus demonstrated an upregulation of crucial immune genes (viperin, IKKB, CCL5, IL1β, and AP1) as well as the antiviral signaling pathways. Interestingly, this experimental approach revealed contrasting evidence of the antiviral potential of chIFN-λ in both in vivo and in vitro models. Taken together, our data signifies the potential of chIFN-λ as a potent antiviral cytokine and highlights its future possible use as an antiviral therapeutic in poultry.

Highlights

Viral pathogens pose significant threats to the poultry industry around the globe
A pairwise BLAST analysis demonstrated that chicken IFN-λ (chIFN-λ) shares 36%, 34%, 39%, 34% and 33%
The present study investigates the IFN stimulated genes (ISGs) and signaling pathways associated with avian immunity and will bring new horizons to target problematic viral pathogens, e.g., Avian influenza viruses (AIVs), circulating within the poultry industry

Summary

Introduction

Viral pathogens pose significant threats to the poultry industry around the globe. This necessitates the development of novel and alternative antiviral therapies to contain the impacts of pathogens. Avian influenza viruses (AIVs) are a particular threat, which cause severe damage to the poultry industry, especially in developing countries where huge monetary losses are incurred [1,2]. Public health is threatened by AIVs, owing to their zoonotic importance. Active preventive strategies would minimize the risk of viral transmission to humans and benefit the poultry industry. Interferons (IFNs) are pleiotropic functional cytokines with antiviral, antitumor, and natural immune-boosting effects. IFNs play a significant role in eliciting an antiviral state in vertebrates [3]

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