Abstract
Duck Tembusu virus (DTMUV) infection has caused great economic losses to the poultry industry in China, since its first discovery in 2010. Understanding of host anti-DTMUV responses, especially the innate immunity against DTMUV infection, would be essential for the prevention and control of this viral disease. In this study, transcriptomic analysis of duck embryonic fibroblasts (DEFs) infected with DTMUV reveals that several innate immunity-related pathways, including Toll-like, NOD-like, and retinoic acid-inducible gene I (RIG-I)-like receptor signaling pathways, are activated. Further verification by RT-qPCR confirmed that RIG-I, MAD5, TLR3, TLR7, IFN-α, IFN-β, MX, PKR, MHCI, MHCII, IL-1β, IL-6, (IFN-regulatory factor 1) IRF1, VIPERIN, IFIT5, and CMPK2 were up-regulated in cells infected with DTMUV. Through overexpression and knockdown/out of gene expression, we demonstrated that both VIPERIN and IRF1 played an important role in the regulation of DTMUV replication. Overexpression of either one significantly reduced viral replication as characterized by reduced viral RNA copy numbers and the envelope protein expression. Consistently, down-regulation of either one resulted in the enhanced replication of DTMUV in the knockdown/out cells. We further proved that IRF1 can up-regulate VIPERIN gene expression during DTMUV infection, through induction of type 1 IFNs as well as directly binding to and activation of the VIPERIN promoter. This study provides a genome-wide differential gene expression profile in cells infected with DTMUV and reveals an important function for IRF1 as well as several other interferon-stimulated genes in restricting DTMUV replication.
Highlights
Tembusu virus (TMUV) belongs to the genus Flavivirus, family Flaviviridae, Ntaya virus group
The innate immune system is the first line of host defense against infection by pathogenic microorganisms, including Duck Tembusu virus (DTMUV) (Li et al, 2020)
Previous studies have shown that DTMUV is mainly recognized by TLR3 and MDA5, resulting in the induction of IFNs and various other antiviral proteins (Yu et al, 2018)
Summary
Tembusu virus (TMUV) belongs to the genus Flavivirus, family Flaviviridae, Ntaya virus group. In 2010, a novel duck disease characterized by acute egg-drop, depression, growth retardation and neurologic signs was emerged, and duck Tembusu virus (DTMUV) was confirmed to be the causative agent of the disease (Chen et al, 2014). DTMUV-infected ducks are frequently followed by a secondary bacterial infection, and the mortality can reach 5–20% (Su et al, 2011). Because of the zoonotic nature of Flaviviruses, DTMUV may cause a public health concern. The virus can infect both avian and mammalian cells, and a number of people worked in the duck industry in China have shown seropositive to DTMUV (Tang et al, 2013a; Yu et al, 2018)
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