The c-Jun N-terminal kinase (JNK) is involved in H5N1 influenza A virus RNA and protein synthesis

Zhang, Shouping; Tian, Haiyan; Cui, Jingmin; Xiao, Jin; Wang, Ming; Hu, Yanxin

doi:10.1007/s00705-015-2668-8

Cited by 23 publications

(26 citation statements)

References 20 publications

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“…NF-κB, mainly p65/p50, activation during SeV and RSV infections occurs through IκB kinase (IKK)-dependent phosphorylation of the NF-κB inhibitor protein IκBα and of the p65 subunit 18 , 19 . The signaling cascade leading to AP-1 activation is more elusive, but ultimately results in the phosphorylation of the nuclear Activating Transcription Factor 2 (ATF-2) and c-Jun subunits by JNK and p38 Mitogen-Activated Protein Kinases (MAPKs) 10 , 20 , 21 . The activation of these transcription factors promotes the transcription of early antiviral genes, type I/III IFNs and proinflammatory cytokines and chemokines 12 , 22 , 23 .…”

Section: Introductionmentioning

confidence: 99%

DUSP1 regulates apoptosis and cell migration, but not the JIP1-protected cytokine response, during Respiratory Syncytial Virus and Sendai Virus infection

Robitaille

Caron

Zucchini

et al. 2017

Sci Rep

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The host antiviral response involves the induction of interferons and proinflammatory cytokines, but also the activation of cell death pathways, including apoptosis, to limit viral replication and spreading. This host defense is strictly regulated to eliminate the infection while limiting tissue damage that is associated with virus pathogenesis. Post-translational modifications, most notably phosphorylation, are key regulators of the antiviral defense implying an important role of protein phosphatases. Here, we investigated the role of the dual-specificity phosphatase 1 (DUSP1) in the host defense against human respiratory syncytial virus (RSV), a pathogenic virus of the Pneumoviridae family, and Sendai virus (SeV), a model virus being developed as a vector for anti-RSV vaccine. We found that DUSP1 is upregulated before being subjected to proteasomal degradation. DUSP1 does not inhibit the antiviral response, but negatively regulates virus-induced JNK/p38 MAPK phosphorylation. Interaction with the JNK-interacting protein 1 scaffold protein prevents dephosphorylation of JNK by DUSP1, likely explaining that AP-1 activation and downstream cytokine production are protected from DUSP1 inhibition. Importantly, DUSP1 promotes SeV-induced apoptosis and suppresses cell migration in RSV-infected cells. Collectively, our data unveils a previously unrecognized selective role of DUSP1 in the regulation of tissue damage and repair during infections by RSV and SeV.

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Section: Introductionmentioning

confidence: 99%

DUSP1 regulates apoptosis and cell migration, but not the JIP1-protected cytokine response, during Respiratory Syncytial Virus and Sendai Virus infection

Robitaille

Caron

Zucchini

et al. 2017

Sci Rep

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“…Phage display has been successfully used to identify epitopes of different viruses such as foot-and-mouth disease virus (FMDV) [23,24], classical swine fever virus (CSFV) [25], Japanese encephalitis virus (JEV) [26], Epstein-Barr virus (EBV) [27], porcine reproductive and respiratory syndrome virus (PRRSV) [28] and mouse hepatitis virus (MHV) [29]. Therefore, one purpose of this study was to identify potential antigenic epitopes in PEDV S1 protein using this technique.…”

Section: Discussionmentioning

confidence: 99%

Putative phage-display epitopes of the porcine epidemic diarrhea virus S1 protein and their anti-viral activity

Cao

Gao

et al. 2015

Virus Genes

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Porcine epidemic diarrhea virus (PEDV) is a pathogen of swine that causes severe diarrhea and dehydration resulting in substantial morbidity and mortality in newborn piglets. Phage display is a technique with wide application, in particular, the identification of key antigen epitopes for the development of therapeutic and diagnostic reagents and vaccines. To identify antigen epitopes with specificity for PEDV, a monoclonal antibody (MAb-5E12) against the immunodominant region of the PEDV Spike protein (S1) was used as the target for biopanning a 12-mer phage display, random peptide library. After multiple rounds of biopanning and stringent washing, three phage-displayed peptides, designated L, W and H, were identified that recognize MAb-5E12. Sequence analysis showed that the one or more of the peptides exhibited partial sequence similarity to the native S1 sequence 'MQYVYTPTYYML' (designated peptide M) at position 201-212. In combination with software analysis for the prediction of B cell epitopes, aa 201-212 exhibited characteristics of a linear epitope on the PEDV S1 protein. In contrast to peptide M, a consensus motif 'PxxY' was identified on both peptides L and W, and on the S1 protein, but not on peptide H. Peptide M and the MAb-5E12-recognizing peptides L and W significantly inhibited the adsorption of PEDV on the cell surface as monitored through plaque-reduction assays. Furthermore, data from real-time PCR and indirect immunofluorescence assays were consistent with the ability of peptides M, L and W to block viral protein expression and thereby function as antiviral agents for PEDV.

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“…Further development of JJ3297 has resulted in the generation of another compound: A22 and NS1 inhibitors are now being investigated in in vivo models of infection ( 89 ). Additionally, SP600125, a C-Jun-N-terminal kinase inhibitor reduces the replication of IV in vitro and in vivo by indirect inhibition of NS1-mediated functions in the early stages of infection ( 90 ) and small molecules such as polyphenol and quinoxaline derivatives have also been proposed to inhibit NS1 ( 91 ). More study is required to determine if NS1 inhibitors are suitable for clinical use.…”

Section: Direct Targeting Of IVmentioning

confidence: 99%

Treating Influenza Infection, From Now and Into the Future

Davidson

2018

Front. Immunol.

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Influenza viruses (IVs) are a continual threat to global health. The high mutation rate of the IV genome makes this virus incredibly successful, genetic drift allows for annual epidemics which result in thousands of deaths and millions of hospitalizations. Moreover, the emergence of new strains through genetic shift (e.g., swine-origin influenza A) can cause devastating global outbreaks of infection. Neuraminidase inhibitors (NAIs) are currently used to treat IV infection and act directly on viral proteins to halt IV spread. However, effectivity is limited late in infection and drug resistance can develop. New therapies which target highly conserved features of IV such as antibodies to the stem region of hemagglutinin or the IV RNA polymerase inhibitor: Favipiravir are currently in clinical trials. Compared to NAIs, these treatments have a higher tolerance for resistance and a longer therapeutic window and therefore, may prove more effective. However, clinical and experimental evidence has demonstrated that it is not just viral spread, but also the host inflammatory response and damage to the lung epithelium which dictate the outcome of IV infection. Therapeutic regimens for IV infection should therefore also regulate the host inflammatory response and protect epithelial cells from unnecessary cell death. Anti-inflammatory drugs such as etanercept, statins or cyclooxygenase enzyme 2 inhibitors may temper IV induced inflammation, demonstrating the possibility of repurposing these drugs as single or adjunct therapies for IV infection. IV binds to sialic acid receptors on the host cell surface to initiate infection and productive IV replication is primarily restricted to airway epithelial cells. Accordingly, targeting therapies to the epithelium will directly inhibit IV spread while minimizing off target consequences, such as over activation of immune cells. The neuraminidase mimic Fludase cleaves sialic acid receptors from the epithelium to inhibit IV entry to cells. While type III interferons activate an antiviral gene program in epithelial cells with minimal perturbation to the IV specific immune response. This review discusses the above-mentioned candidate anti-IV therapeutics and others at the preclinical and clinical trial stage.

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The c-Jun N-terminal kinase (JNK) is involved in H5N1 influenza A virus RNA and protein synthesis

Cited by 23 publications

References 20 publications

DUSP1 regulates apoptosis and cell migration, but not the JIP1-protected cytokine response, during Respiratory Syncytial Virus and Sendai Virus infection

DUSP1 regulates apoptosis and cell migration, but not the JIP1-protected cytokine response, during Respiratory Syncytial Virus and Sendai Virus infection

Putative phage-display epitopes of the porcine epidemic diarrhea virus S1 protein and their anti-viral activity

Treating Influenza Infection, From Now and Into the Future

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