The Leader Protein of Theiler's Virus Prevents the Activation of PKR

Borghese, Fabian; Sorgeloos, Frédéric; Cesaro, Teresa; Michiels, Thomas

doi:10.1128/jvi.01010-19

Cited by 21 publications

(25 citation statements)

References 52 publications

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“…TMEV L pro disrupts PKR function by preventing the interaction between PKR and viral dsRNA during virus infection, thus, inhibiting the consequent PKR-mediated eIF2α phosphorylation and antiviral response. Interestingly, this study found that TMEV L pro did not directly interact with either dsRNA or PKR, and the exact mechanism remains unknown [88].…”

Section: Evasion or Targeting Of Isgsmentioning

confidence: 70%

Innate immune evasion by picornaviruses

Zhang¹,

Paget

Wang³

et al. 2020

Eur J Immunol

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The family Picornaviridae comprises a large number of viruses that cause disease in broad spectrum of hosts, which have posed serious public health concerns worldwide and led to significant economic burden. A comprehensive understanding of the virus‐host interactions during picornavirus infections will help to prevent and cure these diseases. Upon picornavirus infection, host pathogen recognition receptors (PRRs) sense viral RNA to activate host innate immune responses. The activated PRRs initiate signal transduction through a series of adaptor proteins, which leads to activation of several kinases and transcription factors, and contributes to the consequent expression of interferons (IFNs), IFN‐inducible antiviral genes, as well as various inflammatory cytokines and chemokines. In contrast, to maintain viral replication and spread, picornaviruses have evolved several elegant strategies to block innate immune signaling and hinder host antiviral response. In this review, we will summarize the recent progress of how the members of family Picornaviridae counteract host immune response through evasion of PRRs detection, blocking activation of adaptor molecules and kinases, disrupting transcription factors, as well as counteraction of antiviral restriction factors. Such knowledge of immune evasion will help us better understand the pathogenesis of picornaviruses, and provide insights into developing antiviral strategies and improvement of vaccines.

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Section: Evasion or Targeting Of Isgsmentioning

confidence: 70%

Innate immune evasion by picornaviruses

Zhang¹,

Paget

Wang³

et al. 2020

Eur J Immunol

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“…Some viruses evolved various strategies to block SG formation during infection, which counteracted its antiviral effects ( 13 , 20 , 36 , 37 ). And some viruses exploited SG components to facilitate their replication ( 16 , 38 ).…”

Section: Discussionmentioning

confidence: 99%

“…Picornavirus 3C or L protein inhibited SG assembly via targeting G3BP1 for cleavage ( 29 , 40 , 41 ). TMEV L protein prevented the activation of PKR via dampening the responsiveness of PKR to dsRNA, thus inhibiting SG formation ( 36 ). To our surprise, no cleavage band was detected when 293T cells were co-transfected with 3C and G3BP1 ( Figure 7B ).…”

Section: Discussionmentioning

confidence: 99%

Seneca Valley Virus 3C Protease Inhibits Stress Granule Formation by Disrupting eIF4GI-G3BP1 Interaction

et al. 2020

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Stress granules (SGs) are the sites of mRNA storage and related to the regulation of mRNA translation, which are dynamic structures in response to various environmental stresses and viral infections. Seneca Valley virus (SVV), an oncolytic RNA virus belonging to Picornaviridae family, can cause vesicular disease (VD) indistinguished from foot-and-mouth disease (FMD) and other pig VDs. In this study, we found that SVV induced SG formation in the early stage of infection in a PKR-eIF2α dependent manner, as demonstrated by the recruitment of marker proteins of G3BP1 and eIF4GI. Surprisingly, we found that downregulating SG marker proteins TIA1 or G3BP1, or expressing an eIF2α non-phosphorylatable mutant inhibited SG formation, but this inhibition of transient SG formation had no significant effect on SVV propagation. Depletion of G3BP1 significantly attenuated the activation of NF-κB signaling pathway. In addition, we found that SVV inhibited SG formation at the late stage of infection and 3C protease was essential for the inhibition depending on its enzyme activity. Furthermore, we also found that 3C protease blocked the SG formation by disrupting eIF4GI-G3BP1 interaction. Overall, our results demonstrate that SVV induces transient SG formation in an eIF2α phosphorylation and PKR-dependent manner, and that 3C protease inhibits SG formation by interfering eIF4GI-G3BP1 interaction.

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“…Host 463 suppression by multifunctional viral proteins is a critical determinant of success for all RNA 464 viruses [51], including Human Immunodeficiency Virus (HIV) [81]. Viral RNAs can suppress 465 host RNA interference pathways involved in antiviral immunity [82] or block the abilities of host 466 antiviral proteins to engage with viral dsRNAs and mount an immune response [83]. 467…”

Section: Evolutionary Patterns 428mentioning

confidence: 99%

Genomic and immunogenic changes over the history of the Viral Hemorrhagic Septicemia (VHS-IVb) fish virus (=Piscine novirhabdovirus) in the Laurentian Great Lakes

Stepien

Niner

Gorgoglione

et al. 2020

Preprint

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26 27 Viral Hemorrhagic Septicemia Virus (VHSV) (=Piscine novirhabdovirus) appeared in the 28 Laurentian Great Lakes in 2005, constituting a unique and highly virulent genogroup (IVb), 29 which killed >32 fish species in large 2005 and 2006. Periods of apparent dormancy punctuated 30 smaller outbreaks in 2007, 2008, and 2017. We conducted the first whole genome analysis of 31 IVb, evaluating its evolutionary changes using 46 isolates, in reference to immunogenicity in cell 32 culture, and the genomes of other VHS genogroups (I-IVa) and other Novirhabdoviruses. IVb 33 isolates had 253 genomic nucleotide substitutions (2.3% of the total 11,158 nucleotides), with 85 34 (16.6%) being non-synonymous. The greatest number of substitutions occurred in the non-35 coding region (NCDS; 4.3%) followed by the Nv-(3.8%), and M-(2.8%) genes. The M-gene 36 possessed the greatest proportions of amino acid changes (52.9%), followed by the Nv-(50.0%), 37G-(48.6%), N-(35.7%) and L-(23.1%) genes. Among VHS genogroups, IVa from the 38 northeastern Pacific exhibited the fastest substitution rate (2.01x10-3), followed by IVb 39 (6.64x10 -5), and I/III from Europe (4.09x10 -5). A 2016 gizzard shad isolate from Lake Erie was 40 the most divergent IVb isolate (38 NT, 15.0%, 15 AA), yet exhibited reduced virulence with in 41 vitro immunogenicity analyses, as did other 2016 isolates, in comparison to the first IVb isolate 42 (2003). The 2016 isolates exhibited lower impact on innate antiviral responses, suggesting 43 phenotypic effects. Results suggest continued sequence change and lower virulence over the 44 history of IVb, which may facilitate its long-term persistence in fish host populations. 45 46

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The Leader Protein of Theiler's Virus Prevents the Activation of PKR

Cited by 21 publications

References 52 publications

Innate immune evasion by picornaviruses

Innate immune evasion by picornaviruses

Seneca Valley Virus 3C Protease Inhibits Stress Granule Formation by Disrupting eIF4GI-G3BP1 Interaction

Genomic and immunogenic changes over the history of the Viral Hemorrhagic Septicemia (VHS-IVb) fish virus (=Piscine novirhabdovirus) in the Laurentian Great Lakes

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