Innate immune responses to duck Tembusu virus infection

Li, Ning; Zhao, Jingpeng; Yang, Yanjie; Zeng, Yongqing; Liu, Sidang

doi:10.1186/s13567-020-00814-9

Cited by 18 publications

(11 citation statements)

References 148 publications

(178 reference statements)

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“…The innate immune system is the first line of host defense against infection by pathogenic microorganisms, including 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 ).…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic Analysis and Functional Characterization Reveal the Duck Interferon Regulatory Factor 1 as an Important Restriction Factor in the Replication of Tembusu Virus

et al. 2020

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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 upregulated 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.

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Section: Discussionmentioning

confidence: 99%

Transcriptomic Analysis and Functional Characterization Reveal the Duck Interferon Regulatory Factor 1 as an Important Restriction Factor in the Replication of Tembusu Virus

et al. 2020

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“…In particular, changes in the phosphorylation levels of NF-κB, as well as MyD88, receptor interacting protein 1 (RIP1), MDA5, and IRF7, indicated an important role of protein phosphorylation in duck immune responses to viral antigens [ 329 ]. Pattern recognition receptor signaling during innate responses to influenza A viruses in the mallard duck was recently reviewed [ 330 ], and the fundamental roles of NF-κB in innate immune responses to duck Tembusu virus infection were discussed in detail [ 331 ].…”

Section: Effect Of Various Stress Factors On Nf-κb Expression and mentioning

confidence: 99%

Redox Homeostasis in Poultry: Regulatory Roles of NF-κB

2021

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Redox biology is a very quickly developing area of modern biological sciences, and roles of redox homeostasis in health and disease have recently received tremendous attention. There are a range of redox pairs in the cells/tissues responsible for redox homeostasis maintenance/regulation. In general, all redox elements are interconnected and regulated by various means, including antioxidant and vitagene networks. The redox status is responsible for maintenance of cell signaling and cell stress adaptation. Physiological roles of redox homeostasis maintenance in avian species, including poultry, have received limited attention and are poorly characterized. However, for the last 5 years, this topic attracted much attention, and a range of publications covered some related aspects. In fact, transcription factor Nrf2 was shown to be a master regulator of antioxidant defenses via activation of various vitagenes and other protective molecules to maintain redox homeostasis in cells/tissues. It was shown that Nrf2 is closely related to another transcription factor, namely, NF-κB, responsible for control of inflammation; however, its roles in poultry have not yet been characterized. Therefore, the aim of this review is to describe a current view on NF-κB functioning in poultry with a specific emphasis to its nutritional modulation under various stress conditions. In particular, on the one hand, it has been shown that, in many stress conditions in poultry, NF-κB activation can lead to increased synthesis of proinflammatory cytokines leading to systemic inflammation. On the other hand, there are a range of nutrients/supplements that can downregulate NF-κB and decrease the negative consequences of stress-related disturbances in redox homeostasis. In general, vitagene–NF-κB interactions in relation to redox balance homeostasis, immunity, and gut health in poultry production await further research.

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“…DTMUV possesses a genome approximately 11 kb long that encodes three structural proteins (C, prM, and E) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) (7). Whereas the structural proteins primarily mediate the virus' life cycle and fusion in the formation of viral particles (8,9), the non-structural ones engage in viral replication, virion assembly, and innate immune evasion (10). NS3 is a multifunctional protein with three different activities, which are determined by serine protease, RNA helicase, and triphosphatase, respectively (11).…”

Section: Introductionmentioning

confidence: 99%

Non-Structural Protein 3 of Duck Tembusu Virus Induces Autophagy via the ERK and PI3K–AKT–mTOR Signaling Pathways

et al. 2022

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Despite autophagy’s pivotal role in the replication of viruses such as duck Tembusu virus (DTMUV), which has caused massive economic losses to the poultry industry in the world, the specific relationships between DTMUV and cellular autophagy remain largely unknown. In response, we investigated the interactions between autophagy and DTMUV, the effects of the structural and non-structural proteins of DTMUV on autophagy, and the autophagy-related signaling pathways induced by DTMUV. Among the results, DTMUV increased the autophagy flux in duck embryo fibroblasts (DEF) and BHK-21 cells, while autophagy facilitated viral replication. After we pharmacologically induced autophagy with rapamycin (RAPA), the replication of DTMUV increased by 15.23-fold compared with the control group of DEF cells. To identify which DTMUV protein primarily induced autophagy, all three structural proteins and seven non-structural proteins of DTMUV were transfected into cells, and the results showed that non-structural protein 3 (NS3) induced significant autophagy in DEF cells. By means of Western blot, immunofluorescence, and transmission electron microscopy, we confirmed that NS3 protein could significantly induce autophagy and autophagy flux. Furthermore, we showed that NS3 induced autophagy in DEF cells through extracellular signal-regulated kinase 2 (ERK2) and phosphatidylinositol-3-kinase (PI3K)/AKT and the mammalian target of rapamycin (mTOR) signaling pathways using specific inhibitors and RNA interference assays. Finally, autophagy induced by NS3 promoted DTMUV replication. These results provide novel insight into the relationship between DTMUV and autophagy, broadening the current understanding of the molecular pathogenesis of DTMUV.

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Innate immune responses to duck Tembusu virus infection

Cited by 18 publications

References 148 publications

Transcriptomic Analysis and Functional Characterization Reveal the Duck Interferon Regulatory Factor 1 as an Important Restriction Factor in the Replication of Tembusu Virus

Transcriptomic Analysis and Functional Characterization Reveal the Duck Interferon Regulatory Factor 1 as an Important Restriction Factor in the Replication of Tembusu Virus

Redox Homeostasis in Poultry: Regulatory Roles of NF-κB

Non-Structural Protein 3 of Duck Tembusu Virus Induces Autophagy via the ERK and PI3K–AKT–mTOR Signaling Pathways

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