Duck Enteritis Virus VP16 Antagonizes IFN-β-Mediated Antiviral Innate Immunity.

Yang Li,Xumin Ou,Sai Mao,Anchun Cheng,Ling Zhang,Qiao Yang,Yunya Liu,Dekang Zhu,Mafeng Liu,Xiaoyue Chen,Leichang Pan,Bin Tian,Renyong Jia,Shaqiu Zhang,Shun Chen,Juan Huang,Yanling Yu,Mingshu Wang,Xinxin Zhao,Mujeeb Ur Rehman

doi:10.1155/2020/9630452

Yang Li, Xumin Ou + Show 18 more

Open Access

https://doi.org/10.1155/2020/9630452

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Abstract

Duck enteritis virus (DEV) can successfully evade the host innate immune responses and establish a lifelong latent infection in the infected host. However, the study about how DEV escapes host innate immunity is still deficient up to now. In this study, for the first time, we identified a viral protein VP16 by which DEV can obviously downregulate the production of IFN-β in duck embryo fibroblast (DEF). Our results showed that ectopic expression of VP16 decreased duck IFN-β (duIFN-β) promoter activation and significantly inhibited the mRNA transcription of IFN-β. Further study showed that VP16 can also obviously inhibit the mRNA transcription of interferon-stimulated genes (ISGs), such as myxovirus resistance protein (Mx) and interferon-induced oligoadenylate synthetase-like (OASL). Furthermore, we found that this anti-interferon activity of VP16 depended on its N-terminus (aa1-200). Coexpression analysis revealed that VP16 selectively blocked duIFN-β promoter activity at the duIRF7 level rather than duIRF1. Based on the results of coimmunoprecipitation analysis (co-IP) and indirect immunofluorescence assay (IFA), VP16 was able to bind to duck IRF7 (duIRF7) directly, but did not interact with duck IRF1 (duIRF1) in vitro.

Highlights

Duck enteritis virus (DEV) is a kind of enveloped, large DNA virus who belongs to α-herpesvirus
In consideration of cGAS acting as the most effective cytosolic exogenous DNA sensing in most DNA viruses [77], I ventured a guess whether DEV is involved in the cGAS-STING-mediated pathway
By using Dual-Luciferase Reporter Gene System, I found that DEV could inhibit duck IFN-β promoter activity that was upregulated by ectopic expression of duck cGAS and STING (Figure 1(b))

Summary

Introduction

Duck enteritis virus (DEV) is a kind of enveloped, large DNA virus who belongs to α-herpesvirus. As a prevalent pathogen spreading in waterfowl, it causes acute fever and septic disease in some cases. In the chronic cases, DEV contributes to latent infections in the TG (trigeminal ganglia) after establishing a primary infection. In common with other members of α-herpesvirus family, DEV possesses the ability to establish latency in the sensory ganglia and lymphoid tissues [27]. The innate immune system plays an essential role in defending the host against viral infection They could detect the presence of pathogens and initiate relevant mechanisms to eliminate potentially infectious threats. PRRs recognize conserved features of viruses and other microorganisms They were investigated and known as PAMPs (pathogen-associated molecular patterns), which include microbial nucleic acids, proteins, and carbohydrates. PAMPs own key molecular characteristics shared by classes of pathogens are usually absent from healthy cells [31]

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