Cherry Valley Ducks Mitochondrial Antiviral-Signaling Protein-Mediated Signaling Pathway and Antiviral Activity Research.

Ning Li,Tianqi Hong,Zongxi Cao,Rong Li,Tongjie Chai,Mengjiao Guo,Yumei Cai,Sidang Liu,Yao Wang,Liangmeng Wei

doi:10.3389/fimmu.2016.00377

Abstract

Mitochondrial antiviral-signaling protein (MAVS), an adaptor protein of retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs)-mediated signal pathway, is involved in innate immunity. In this study, Cherry Valley duck MAVS (duMAVS) was cloned from the spleen and analyzed. duMAVS was determined to have a caspase activation and recruitment domain at N-terminal, followed by a proline-rich domain and a transmembrane domain at C-terminal. Quantitative real-time PCR indicated that duMAVS was expressed in all tissues tested across a broad expression spectrum. The expression of duMAVS was significantly upregulated after infection with duck Tembusu virus (DTMUV). Overexpression of duMAVS could drive the activation of interferon (IFN)-β, nuclear factor-κB, interferon regulatory factor 7, and many downstream factors (such as Mx, PKR, OAS, and IL-8) in duck embryo fibroblast cells. What is more, RNA interference further confirmed that duMAVS was an important adaptor for IFN-β activation. The antiviral assay showed that duMAVS could suppress the various viral replications (DTMUV, novel reovirus, and duck plague virus) at early stages of infection. Overall, these results showed that the main signal pathway mediated by duMAVS and it had a broad-spectrum antiviral ability. This research will be helpful to better understanding the innate immune system of ducks.

Highlights

The innate immune response occurs in the early days of infection and functions as the first line of host defense against microbial pathogens
The protein domains were predicated by Sample Modular Architecture Research Toll (SMART) program and the results indicated that duck MAVS (duMAVS) contained three characteristic domains: a caspase activation and recruitment domains (CARDs)-like domain at its N-terminus, a central proline-rich domain and a hydrophobic TM domain at its C-terminus (Figure 1A)
A phylogenetic tree was generated based on the full length of Mitochondrial antiviral-signaling protein (MAVS), and the results showed that there were three major branches (Figure 1B). duMAVS and other birds MAVSs were in the same subgroup, which is confirmed by the high bootstrap values

Summary

Introduction

The innate immune response occurs in the early days of infection and functions as the first line of host defense against microbial pathogens. The pattern recognition receptors (PRRs) play a central role in detecting the pathogen-associated molecular patterns (PAMPs). The recognition of PAMPs initiates the innate immune response to microorganism, which is characterized by the induction of interferons (IFNs), IFN-stimulated genes (ISGs), and proinflammatory cytokines [1, 2]. RIG-I possesses two N-terminal caspase activation and recruitment domains (CARDs), these domains send the signals to downstream signaling molecules, followed by a central RNA helicase domain and a transmembrane (TM) domain at C-terminal, which are responsible for binding viral RNA [3]. Upon activation of RIG-I and MDA5, CARD will recruit an adaptor protein that is located in the mitochondria to phosphorylate transcription molecular nuclear factor (NF)-κB and IFN regulatory factor 3/7 (IRF3/7), and induce the expression of cytokines, resulting in the establishment of innate immune response and the development of adaptive immunity [3]

Methods

Results

Conclusion