Goose Mx and OASL Play Vital Roles in the Antiviral Effects of Type I, II, and III Interferon against Newly Emerging Avian Flavivirus.

Shun Chen,Ying Wu,Qiao Yang,Xiaoyue Chen,Jinyue Zhang,Anchun Cheng,Dekang Zhu,Renyong Jia,Wei Zhang,Mingshu Wang,Mafeng Liu,Zhen Wu,Kunfeng Sun

doi:10.3389/fimmu.2017.01006

Abstract

Duck Tembusu virus (TMUV), an emerging avian flavivirus, is highly pathogenic to birds and has the potential to become a zoonotic pathogen. Here, the molecular antiviral mechanism of goose type I, II, and III interferon (goIFNα, goIFNγ, and goIFNλ), the key components of the innate immune pathway, against TMUV was studied. We found that the transcription of goIFNs was obviously driven by TMUV infection in vivo and in vitro, and the titers and copies of TMUV were significantly reduced following treatment with goIFNs. The results of RNA sequencing (RNA-seq) revealed that goIFN stimulation triggered a set of differentially expressed genes at different levels and a positive regulatory feedback loop of IFN release against infection. Two important interferon-stimulated genes, goMx and goOASL, were identified as workhorse IFNs in the inhibition of TMUV replication. The antiviral effects of goMx and goOASL were confirmed by transient overexpression and knockdown assay in vitro. Overall, our findings defined that goose Mx and OASL play key roles in the antiviral effects of type I, II, and III interferon against the TMUV. These results extend our understanding of the transcriptional profile of the goose IFN-mediated signaling pathway and provide insight into the antiviral mechanism of goIFNs against flavivirus infection.

Highlights

In the classical innate immune pathway, incoming viral pathogens are sensed by cytologic host pattern recognition receptors, which activates downstream interferon regulatory factors (IRFs), leading to subsequent IFN production [1, 2]
RT-qPCR analysis showed that the overexpression of goMx or goOASL obviously reduced the TMUV replication, while the antiviral effect was reduced by the silencing of goMx and goOASL expression at 36 hpi, respectively (Figures 10A,B). These results indicated that goMx and goOASL conferred substantial protection against TMUV infection
The results demonstrated that knockdown of goMx and goOASL significantly impaired the antiviral response of goIFNs against TMUV infection in vitro (Figures 10C–E)

Summary

Introduction

In the classical innate immune pathway, incoming viral pathogens are sensed by cytologic host pattern recognition receptors (such as toll-like receptors, RIG-I-like receptors, NOD-like receptors), which activates downstream interferon regulatory factors (IRFs), leading to subsequent IFN production [1, 2]. Interferons (IFNs) are cytokines with important antiviral activities and represent a powerful barrier to viral infection [3, 4]; IFNs bind their cognate receptors and subsequently initiate a signaling cascade through the Janus kinase signal transducer and activator of transcription (JAK-STAT) pathway, triggering the expression of hundreds of IFN-stimulated genes (ISGs) [5, 6]. These ISGs are mainly classified into three groups, positive regulators, negative regulators, and antiviral effectors, based on the numerous regulation mechanisms of innate immune signaling [7]. It is well known that Mx1, OAS1, and PKR are potent antiviral effectors involved in the inhibition of viral infection [13,14,15]

Methods

Results

Discussion

Conclusion