Avian Tembusu virus infection effectively triggers host innate immune response through MDA5 and TLR3-dependent signaling pathways.

Shilong Chen,Guifeng Luo,Song Wang,Xiancheng Zeng,Shaoying Chen,Zhou Yang,Ji-Long Chen,Shuncheng Lin,Xiaojuan Chi,Mohsan Ullah Goraya

doi:10.1186/s13567-016-0358-5

Abstract

Avian Tembusu virus (ATMUV) is a newly emerged flavivirus that belongs to the Ntaya virus group. ATMUV is a highly pathogenic virus causing significant economic loss to the Chinese poultry industry. However, little is known about the role of host innate immune mechanism in defending against ATMUV infection. In this study, we found that ATMUV infection significantly up-regulated the expression of type I and type III interferons (IFN) and some critical IFN-stimulated genes (ISG) in vivo and in vitro. This innate immune response was induced by genomic RNA of ATMUV. Furthermore, we observed that ATMUV infection triggered IFN response mainly through MDA5 and TLR3-dependent signaling pathways. Strikingly, shRNA-based disruption of IPS-1, IRF3 or IRF7 expression significantly reduced the production of IFN in the 293T cell model. Moreover, NF-κB was shown to be activated in both chicken and human cells during the ATMUV infection. Inhibition of NF-κB signaling also resulted in a clear decrease in expression of IFN. Importantly, experiments revealed that treatment with IFN significantly impaired ATMUV replication in the chicken cell. Consistently, type I IFN also exhibited promising antiviral activity against ATMUV replication in the human cell. Together, these data indicate that ATMUV infection triggers host innate immune response through MDA5 and TLR3-dependent signaling that controls IFN production, and thereby induces an effective antiviral immunity.Electronic supplementary materialThe online version of this article (doi:10.1186/s13567-016-0358-5) contains supplementary material, which is available to authorized users.

Highlights

Avian Tembusu virus (ATMUV), a newly emerged flavivirus, is the causative agent of acute egg-drop syndrome in domestic poultry of China since 2009 [1,2,3,4]
We found that ATMUV infection resulted in significant up-regulation of mRNA levels of type I and type III IFN in vivo and in vitro mainly through melanoma differentiation associated protein 5 (MDA5) and TLR3 dependent signaling pathways
ATMUV infection induces robust expression of particular type I and type III IFN and some critical IFN-stimulated genes (ISG) in chicken embryo fibroblasts To determine whether ATMUV infection could trigger host innate immune response, chicken embryo fibroblasts (CEF) were infected with ATMUV CJD05 strain at multiplicity of infection (MOI) of 1.0, harvested at different time points post infection, and examined for expression of ATMUV, IFN

Summary

Introduction

Avian Tembusu virus (ATMUV), a newly emerged flavivirus, is the causative agent of acute egg-drop syndrome in domestic poultry of China since 2009 [1,2,3,4]. Chen et al Vet Res (2016) 47:74 structure of the pathogen, which are known as pathogen associated molecular patterns (PAMP) via pattern recognition receptors (PRR) Such receptors include Toll-like receptors (TLR), the RIG-I like receptors (RLR) and NOD like receptors (NLR) [10]. Particular PRR that contain caspase-recruiting domains (CARD), interacts with interferon-β promoter stimulator-1 (IPS-1, known as VISA, MAVS or Cardif ) through CARD–CARD interaction. This interaction activates members of the IKK protein kinase family [15, 16]. The IFN-activated signaling pathway is an important component of the innate immune system and has been implicated in clinical antiviral treatment [22]

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