Host cellular signaling induced by influenza virus

Dai, Xinxian; Zhang, Li-Shu; Hong, Tao

doi:10.1007/s11427-010-4116-z

Cited by 18 publications

(15 citation statements)

References 105 publications

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“…Initiation of inflammatory reaction triggered by viral infection is dependent on several signaling cascades, including NF-κB and MAPKs (ERK1/2 and P38 MAPK). It's well-recognized that the interaction between virus-derived pathogen-associated molecular patterns (PAMPs) and cellular specialized pattern recognition receptors (PPRs) leads to IKBα/NF-κB dissociation and thus released NF-κB translocates into nucleus, where it regulates the transcription of pro-inflammatory mediators, including TNFα, IL-6, IL-8 and COX-2 [19]. Recent studies in vitro and in vivo revealed that massive induction of proinflammatory mediators in H5N1-infected patients was NF-κB-dependent [20,21].…”

Section: Introductionmentioning

confidence: 99%

Sinensetin suppresses influenza a virus-triggered inflammation through inhibition of NF-κB and MAPKs signalings

Xiang

Liang

et al. 2020

BMC Complement Med Ther

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Background: Human respiratory system infected with influenza A virus (IAV) elicited a robust pro-inflammatory response that resulted in severe illness and even death. Currently, limited immunomodulator is available to counteract IAV-associated pneumonia in the clinic. Sinensetin, a polymethoxylated flavone with five methoxy groups, has been found to possess anti-agiogenesis, anti-inflammatory and anti-diabetic activities. However, the effects of sinensetin on IAV-triggered pro-inflammatory response remain unclear. In the present study, the antiinflammatory effects and corresponding possible mechanism of sinensetin in IAV-infected A549 cells were subjected to investigations.Methods: The cytotoxic effects of sinensetin towards A549 cells was detected by MTT and LDH assays. The antiviral activity of sinensetin against influenza A virus was assayed in A549 cells with an engineered replication-competent influenza A virus carrying Gaussia luciferase reporter gene infection. The effect of sinensetin on influenza A virustriggered inflammatory reaction was determined by qRT-PCR, Luminex assays, ELISA and Western blot. Results: Our results showed that sinensetin did not exhibit antiviral activity against A/PR/8/34 (H1N1). Meanwhile, sinensetin treatment significantly decreased IAV-induced expression of pro-inflammatory mediators at mRNA and protein levels, including IL-6, TNF-α, IP-10, IL-8 and MCP-1. Additionally, levels of cyclooxygenase (COX)-2 and the downstream product prostaglandin E 2 (PGE 2 ) up-regulated by IAV infection were dramatically suppressed by sinensetin. The mechanistic investigation revealed that sinensetin treatment suppressed the NF-κB transcriptional activity using the NF-κB reporter stable HEK293 cell line stimulated with TNF-α (20 ng/mL) or influenza H1N1 virus. Furthermore, sinensetin abrogated influenza H1N1 virus-induced activation of NF-κB, ERK1/2 MAPK and p38 MAPK signalings.Conclusion: Collectively, our results indicated that sinensetin has potential capacity to attenuate IAV-triggered pro-inflammatory response via inactivation of NF-κB, ERK1/2 MAPK and p38 MAPK signalings, which implied that sinensetin may be a promising candidate drug for influenza H1N1 virus infection therapeutics.

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Section: Introductionmentioning

confidence: 99%

Sinensetin suppresses influenza a virus-triggered inflammation through inhibition of NF-κB and MAPKs signalings

Xiang

Liang

et al. 2020

BMC Complement Med Ther

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“…significant health problem (Dai et al 2011). Type A influenza belongs to the BOrthomyxoviridae family,^a family of RNA viruses that includes five genera: influenza virus A, influenza virus B, influenza virus C, isavirus, and thogotovirus.…”

Section: Introductionmentioning

confidence: 99%

Effect of sesamin against cytokine production from influenza type A H1N1-induced peripheral blood mononuclear cells: computational and experimental studies

Fanhchaksai

Kodchakorn

Pothacharoen

et al. 2015

In Vitro Cell.Dev.Biol.-Animal

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In 2009, swine flu (H1N1) had spread significantly to levels that threatened pandemic influenza. There have been many treatments that have arisen for patients since the WHO first reported the disease. Although some progress in controlling influenza has taken place during the last few years, the disease is not yet under control. The development of new and less expensive anti-influenza drugs is still needed. Here, we show that sesamin from the seeds of the Thai medicinal plant Sesamum indicum has anti-inflammatory cytokines in human peripheral blood mononuclear cells (PBMCs) induced by 2009 influenza virus type A H1N1. In this study, the combinatorial screening method combined with the computational approach was applied to investigate the new molecular binding structures of sesamin against the 2009 influenza virus type A H1N1 (p09N1) crystallized structure. Experimental methods were applied to propose the mechanisms of sesamin against cytokine production from H1N1-induced human PBMC model. The molecular dynamics simulation of sesamin binding with the p09N1 crystallized structure showed new molecular binding structures at ARG118, ILE222, ARG224, and TYR406, and it has been proposed that sesamin could potentially be used to produce anti-H1N1 compounds. Furthermore, the mechanisms of sesamin against cytokine production from influenza type A H1N1-induced PBMCs by ELISA and signaling transduction showed that sesamin exhibits the ability to inhibit proinflammatory cytokines, IL-1β and TNF-α, and to enhance the activity of the immune cell cytokine IL-2 via downregulating the phosphorylated JNK, p38, and ERK1/2 MAPK signaling pathways. This information might very well be useful in the prevention and treatment of immune-induced inflammatory disorders.

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“…Conversely, at late stages of infection (17‐20 hours after infection), the P13K‐Akt pathway is inactivated due to the activation of pro‐apoptotic p53 signaling and its related targets p21/waf . In addition, mitogen‐activated protein kinase (MAPK), which includes the Raf/MEK/ERK pathway, is also activated in association with G protein coupled receptors . The accumulation of p53 signaling cascades and MAPK at late stages of infection stimulates proinflammatory cytokines IL‐1β, IL‐8, tumor necroses factor, interferon gamma, and subsequently activates apoptotic signaling cascades that facilitate virus release .…”

Section: Discussionmentioning

confidence: 99%

“…28 In addition, mitogenactivated protein kinase (MAPK), which includes the Raf/MEK/ ERK pathway, is also activated in association with G protein coupled receptors. 42,43 The accumulation of p53 signaling cascades and MAPK at late stages of infection stimulates proinflammatory cytokines IL-1β, IL-8, tumor necroses factor, interferon gamma, and subsequently activates apoptotic signaling cascades that facilitate virus release. 42,44 Like other viruses, IAV infection induces a serious stress in the host.…”

Section: Discussionmentioning

confidence: 99%

Guava flavonoid glycosides prevent influenza A virus infection via rescue of P53 activity

Khalil

Maksoud

Roshdey

et al. 2018

Journal of Medical Virology

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Influenza is a highly infectious disease caused by three types of viruses, including influenza A virus (IAV), influenza B virus, and, rarely, influenza C virus. IAV is a major, global public health threat, causing approximately 500 000 deaths per year worldwide. The new strains of IAV have emerged due to a mutation called antigenic shift, which results in a new subtype of the virus that shows resistance to common antiviral drugs. Here, guava and lemon extracts, including green leaves and flowers, were investigated for their activity against IAV replication in human A549 cells. Concomitantly, the cytotoxicity of a potent extract on host-cell multiplication was assessed. Our results reveal that guava extracts inhibit IAV replication, indicated by viral nucleoprotein expression profile and traditional plaque assay. Interestingly, treatment with guava extract inactivates Akt protein kinase and stimulates the pro-apoptotic protein P53, at early stages of infection. Furthermore, purified guava flavonoid glycosides (GFGs) show competitive inhibition of IAV-virus replication via early regulation of IL-1β and IL-8 in association with P53 gene expression. The docking analysis of GFGs and the protein structure of upstream targets for the Akt signaling pathway indicates a sufficient interaction and stabilization with Gbr2 protein. These data indicate that treatment with GFGs disturbs IAV replication via activation of P53 and its apoptotic related factors after infection. Collectively, these data show that targeting of essential host kinases that are involved in the replication cycle of IAV and rescue of P53 activity by GFGs could represent a new strategy to eradicate IAV.

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Host cellular signaling induced by influenza virus

Cited by 18 publications

References 105 publications

Sinensetin suppresses influenza a virus-triggered inflammation through inhibition of NF-κB and MAPKs signalings

Sinensetin suppresses influenza a virus-triggered inflammation through inhibition of NF-κB and MAPKs signalings

Effect of sesamin against cytokine production from influenza type A H1N1-induced peripheral blood mononuclear cells: computational and experimental studies

Guava flavonoid glycosides prevent influenza A virus infection via rescue of P53 activity

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