Binding of the Duck Tembusu Virus Protease to STING Is Mediated by NS2B and Is Crucial for STING Cleavage and for Impaired Induction of IFN-β

Wu, Zaohe; Zhang, Wei; Wu, Yong; Wang, Tao; Wu, Shaoxiong; Wang, Mingshu; Jia, Renyong; Zhu, Dekang; Liu, Mafeng; Zhao, Xinxin; Yang, Qiao; Wu, Ying; Zhang, Shaqiu; Liu, Yunya; Zhang, Ling; Yu, Yanling; Pan, Leichang; Merits, Andres; Chen, Shun; Cheng, Anchun

doi:10.4049/jimmunol.1900956

Cited by 47 publications

(49 citation statements)

References 51 publications

(64 reference statements)

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“…The amino acid residues at 164, 167, and 361 in STING were important for NS2A binding with STING [145]. However, NS2B3 polyproteins inhibited IFN induction by hydrolyzing duck STING, and further mapping analysis showed the scissile bond located between the R84 and G85 residues of STING [146]. It is suggested by the immune evasion strategies employed by DTMUV via targeting MAVS and STING were critical for host innate immune responses to DTMUV infection.…”

Section: Inhibition Of Ifn Production By Targeting Important Adaptor mentioning

confidence: 99%

Innate immune responses to duck Tembusu virus infection

Zhao

Yang

et al. 2020

Vet Res

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The disease caused by duck Tembusu virus (DTMUV) is characterized by severe egg-drop in laying ducks. Currently, the disease has spread to most duck-raising areas in China, leading to great economic losses in the duck industry. In the recent years, DTMUV has raised some concerns, because of its expanding host range and increasing pathogenicity, as well as the potential threat to public health. Innate immunity is crucial for defending against invading pathogens in the early stages of infection. Recently, studies on the interaction between DTMUV and host innate immune response have made great progress. In the review, we provide an overview of DTMUV and summarize current advances in our understanding of the interaction between DTMUV and innate immunity, including the host innate immune responses to DTMUV infection through pattern recognition receptors (PRRs), signaling transducer molecules, interferon-stimulated genes (ISGs), and the immune evasion strategies employed by DTMUV. The aim of the review is to gain an in-depth understanding of DTMUV pathogenesis to facilitate future studies.

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Section: Inhibition Of Ifn Production By Targeting Important Adaptor mentioning

confidence: 99%

Innate immune responses to duck Tembusu virus infection

Zhao

Yang

et al. 2020

Vet Res

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“…Although the focus of this review is on the mammalian cytosolic DNA sensory system and the flaviviral strategies on regulation and modulation of those pathways, the authors believe it is noteworthy to mention some elucidating new research coming from the field of avian flavivirus (duck Tembusu virus, or DTMUV) [88,89,137].…”

Section: Duck Tembusu Virusmentioning

confidence: 99%

Innate Immune DNA Sensing of Flaviviruses

Zhu

Fernández-Sesma

2020

Viruses

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Flaviviruses are arthropod-borne RNA viruses that have been used extensively to study host antiviral responses. Often selected just to represent standard single-stranded positive-sense RNA viruses in early studies, the Flavivirus genus over time has taught us how truly unique it is in its remarkable ability to target not just the RNA sensory pathways but also the cytosolic DNA sensing system for its successful replication inside the host cell. This review summarizes the main developments on the unexpected antagonistic strategies utilized by different flaviviruses, with RNA genomes, against the host cyclic GAMP synthase (cGAS)/stimulator of interferon genes (STING) cytosolic DNA sensing pathway in mammalian systems. On the basis of the recent advancements on this topic, we hypothesize that the mechanisms of viral sensing and innate immunity are much more fluid than what we had anticipated, and both viral and host factors will continue to be found as important factors contributing to the host innate immune system in the future.

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“…This single ORF encodes one polyprotein precursor that is subsequently cleaved by viral and cellular proteases into three structural proteins, the capsid (C), precursor membrane (prM) and envelope (E), and seven non-structural proteins (NSs), NS1, NS2A, NS2B, NS3, NS4A, 2KNS4B, and NS5 (Tang et al, 2015;Zhu et al, 2015). In addition to their essential functions in the viral life cycles, both structural and non-structural proteins are probably involved in regulating the innate and adaptive immunity of host cells (Wu et al, 2019).…”

Section: Introductionmentioning

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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Binding of the Duck Tembusu Virus Protease to STING Is Mediated by NS2B and Is Crucial for STING Cleavage and for Impaired Induction of IFN-β

Abstract: This information is current as β Impaired Induction of IFN-Crucial for STING Cleavage and for to STING Is Mediated by NS2B and Is Binding of the Duck Tembusu Virus Protease

Cited by 47 publications

References 51 publications

Innate immune responses to duck Tembusu virus infection

Innate immune responses to duck Tembusu virus infection

Innate Immune DNA Sensing of Flaviviruses

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

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