Phosphorylation of influenza A virus NS1 protein at threonine 49 suppresses its interferon antagonistic activity

Kathum, Omer Abid; Schräder, Tobias; Anhlan, Darisuren; Nordhoff, Carolin; Liedmann, Swantje; Pande, Amit; Mellmann, Alexander; Ehrhardt, Christina; Wixler, Viktor; Ludwig, Stephan

doi:10.1111/cmi.12559

Cited by 32 publications

(29 citation statements)

References 30 publications

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“…This study further demonstrates that the NS1 suppression of RIG-I ubiquitination in mouse is Riplet-dependent (101). Conversely, phosphorylation of NS1 at Thr49 was recently identified as impairing the NS1-TRIM25 interaction, thereby suppressing its antagonistic activity of RIG-I signaling (102). Phosphorylation of another site on NS1, Thr80, has also been reported to disrupt NS1 binding affinity with RIG-I (103).…”

Section: Modulation Of the Ptmssupporting

confidence: 56%

Host and Viral Modulation of RIG-I-Mediated Antiviral Immunity

2017

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Innate immunity is the first line of defense against invading pathogens. Rapid and efficient detection of pathogen-associated molecular patterns via pattern-recognition receptors is essential for the host to mount defensive and protective responses. Retinoic acid-inducible gene-I (RIG-I) is critical in triggering antiviral and inflammatory responses for the control of viral replication in response to cytoplasmic virus-specific RNA structures. Upon viral RNA recognition, RIG-I recruits the mitochondrial adaptor protein mitochondrial antiviral signaling protein, which leads to a signaling cascade that coordinates the induction of type I interferons (IFNs), as well as a large variety of antiviral interferon-stimulated genes. The RIG-I activation is tightly regulated via various posttranslational modifications for the prevention of aberrant innate immune signaling. By contrast, viruses have evolved mechanisms of evasion, such as sequestrating viral structures from RIG-I detections and targeting receptor or signaling molecules for degradation. These virus–host interactions have broadened our understanding of viral pathogenesis and provided insights into the function of the RIG-I pathway. In this review, we summarize the recent advances regarding RIG-I pathogen recognition and signaling transduction, cell-intrinsic control of RIG-I activation, and the viral antagonism of RIG-I signaling.

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Section: Modulation Of the Ptmssupporting

confidence: 56%

Host and Viral Modulation of RIG-I-Mediated Antiviral Immunity

2017

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“…Reporter plasmid pTATA luc-IFN-β (Kathum et al, 2015) has been used to investigate the inhibition of interferon activation by NS1 fusion proteins. Figure 1a).…”

Section: Tamoxifen-induced Apoptosis Was Observed In All Cells Expresmentioning

confidence: 99%

Influenza A virus NS1 protein-induced JNK activation and apoptosis are not functionally linked

Nacken

Wixler

Ehrhardt³

et al. 2017

Cellular Microbiology

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Expression of the influenza A virus (IAV) nonstructural protein (NS1) results in the activation of c-Jun N-terminal kinase (JNK). Both NS1 and JNK are involved in apoptosis induction. To investigate their interrelationship, we stably expressed a tamoxifen inducible NS1 oestrogen receptor fusion-protein (NS1ERT) in mammalian cells. Upon tamoxifen stimulation, NS1ERT-expressing cells partially rescued the attenuated replication of NS1-deficient IAVs and also inhibited interferon up-regulation, confirming the functional competence of NS1ERT. Tamoxifen-induced NS1ERT created a cytopathic phenotype and led to the activation of JNK and apoptosis. Induction of NS1F103SERT mutant failed to activate JNK, but induced apoptosis, whereas the induction of NS1M106IERT led to JNK phosphorylation, but not apoptosis, indicating that JNK activation and apoptosis induction are not functionally linked. Further mutational analysis highlighted that apoptosis induction is a function of the C-terminal effector domain of NS1. Finally, IAVs encoding mutant NS1 revealed a modulating effect of NS1 on apoptosis induction in a genuine infection. With respect to apoptogenicity, an NS1 mutant virus that results in a super activation of JNK behaves similarly to the JNK nonactivating virus expressing NS1F103S, thus confirming that NS1-mediated JNK activation and apoptosis induction are also functionally independent from each other in vivo.

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“…Some diseases such as African swine fever and bovine leukemia only influence animals. But to some epidemic, those pathogenic bacteria can be spilled from domestic animals or wildlife to human beings, and the development and mutation during the transmission will make the pathogenic bacteria difficult to control [4][5][6]. A lot of diseases besetting human beings such as human immunodeficiency virus (HIV), SARS corona virus, Ebola virus and avian influenza viruses (AIV) all can trace their filiation from animals [7].…”

Section: Introductionmentioning

confidence: 99%

State feedback impulsive therapy to SIS model of animal infectious diseases

Liu

Zhang

Chen

2019

Physica A: Statistical Mechanics and its Applications

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h i g h l i g h t s• A state feedback impulsive model is constructed to analyze the treatment of animal epidemics.• The existence of order-1 periodic solution to an impulsive system is proved.• The stability of the order-1 periodic solution is proved with a novel method. a b s t r a c tControlling animal infectious diseases and its related infra microbes is of great significance to public health, since a lot of infectious diseases originate from animal epidemics and they often threaten human health. A state feedback impulsive model is constructed to depict the transmission and treatment of animal epidemics. Basing on the impulsive model, the existence of order-1 periodic solution and its stability are proved with a novel method. The theoretical results indicate that the impulsive treatment triggered by the number of infectious is an efficient approach to control animal infectious disease from breakout. Numerical simulation is presented to support the theoretical conclusion in the end.

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Phosphorylation of influenza A virus NS1 protein at threonine 49 suppresses its interferon antagonistic activity

Cited by 32 publications

References 30 publications

Host and Viral Modulation of RIG-I-Mediated Antiviral Immunity

Host and Viral Modulation of RIG-I-Mediated Antiviral Immunity

Influenza A virus NS1 protein-induced JNK activation and apoptosis are not functionally linked

State feedback impulsive therapy to SIS model of animal infectious diseases

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