Influenza Virus-induced NF-κB-dependent Gene Expression Is Mediated by Overexpression of Viral Proteins and Involves Oxidative Radicals and Activation of IκB Kinase

Flory, Egbert; Kunz, Manfred; Scheller, Carsten; Jassoy, Christian; Stauber, Roland H.; Rapp, Ulf R.; Ludwig, Stephan

doi:10.1074/jbc.275.12.8307

Cited by 131 publications

(101 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A wide variety of microbial pathogens, including M. tuberculosis, enhance production of inflammatory cytokines, such as TNF-␣, IL-6, and IL-8, through up-regulation of transcription factors, particularly NF-B (21,(32)(33)(34)(35). Inhibition of cytokine production by microorganisms through down-regulation of transcription factors has rarely been described.…”

Section: Discussionmentioning

confidence: 99%

Reduced Expression of Nuclear Cyclic Adenosine 5′-Monophospate Response Element-Binding Proteins and IFN-γ Promoter Function in Disease Due to an Intracellular Pathogen

Samten

Ghosh

et al. 2002

The Journal of Immunology

View full text Add to dashboard Cite

Mycobacterium tuberculosis-induced IFN-γ protein and mRNA expression have been shown to be reduced in tuberculosis patients, compared with healthy tuberculin reactors. To determine whether this decrease was associated with reduced activity of the IFN-γ promoter, we first studied binding of nuclear proteins to the radiolabeled proximal IFN-γ promoter (−71 to −40 bp), using EMSAs with nuclear extracts of freshly isolated peripheral blood T cells. Nuclear extracts of T cells from most tuberculosis patients showed markedly reduced expression of proteins that bind to the proximal IFN-γ promoter, compared with findings in nuclear extracts of T cells from healthy tuberculin reactors. These DNA-binding complexes contained CREB proteins, based on competitive EMSAs, supershift assays, and Western blotting with an anti-CREB Ab. Transient transfection of PBLs with a luciferase reporter construct under the control of the IFN-γ promoter revealed reduced IFN-γ promoter activity in tuberculosis patients. Transient transfection of Jurkat cells with a dominant-negative CREB repressor plasmid reduced IFN-γ promoter activity. These data suggest that reduced expression of CREB nuclear proteins in tuberculosis patients results in decreased IFN-γ promoter activity and reduced IFN-γ production.

show abstract

Section: Discussionmentioning

confidence: 99%

Reduced Expression of Nuclear Cyclic Adenosine 5′-Monophospate Response Element-Binding Proteins and IFN-γ Promoter Function in Disease Due to an Intracellular Pathogen

Samten

Ghosh

et al. 2002

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Recently, we identified influenza A virus hemagglutinin, nucleoprotein, and matrix protein as viral transactivators toward the transcription factor NF-B (36). However, expression of these proteins resulted in neither the activation of JNK (data not shown) nor the activation of AP-1-dependent promoters (36). These studies were extended to the viral NS1 and NEP/NS2 proteins, which also did not induce JNK activity when overexpressed (data not shown).…”

Section: Accumulation Of Rna Synthesized By the Viral Polymerase Compmentioning

confidence: 98%

Influenza Virus-induced AP-1-dependent Gene Expression Requires Activation of the JNK Signaling Pathway

Ludwig¹,

Ehrhardt²,

Neumeier

et al. 2001

Journal of Biological Chemistry

Self Cite

145

133

View full text Add to dashboard Cite

“…It is well known that influenza virus infection induces activation of NF-B signaling via different mechanisms (54,55), although the function of NF-B activation in the signaling network is discussed highly controversially. We and others could show that influenza A virus infection is associated with expression of NF-Bdependent gene products such as proinflammatory cytokines in cell culture (6, 53, 56 -58) and in vivo models (59 -61).…”

Section: Discussionmentioning

confidence: 99%

Essential Impact of NF-κB Signaling on the H5N1 Influenza A Virus-Induced Transcriptome

Schmolke¹,

Viemann²,

Roth³

et al. 2009

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Systemic infections of humans and birds with highly pathogenic avian influenza A viruses of the H5N1 subtype are characterized by inner bleedings and a massive overproduction of cytokines known as cytokine storm. Growing evidence supports the role of endothelial cells in these processes. The aim of this study was to elucidate determinants of this strong response in endothelial cells with a focus on the transcription factor NF-κB. This factor is known as a major regulator of inflammatory response; however, its role in influenza virus replication and virus-induced immune responses is controversially discussed. By global mRNA profiling of infected cells in the presence or absence of a dominant negative mutant of IκB kinase 2 that specifically blocks the pathway, we could show that almost all H5N1 virus-induced genes depend on functional NF-κB signaling. In particular, activation of NF-κB is a bottleneck for the expression of IFN-β and thus influences the expression of IFN-dependent genes indirectly in the primary innate immune response against H5N1 influenza virus. Control experiments with a low pathogenic influenza strain revealed a much weaker and less NF-κB-dependent host cell response.

show abstract

Influenza Virus-induced NF-κB-dependent Gene Expression Is Mediated by Overexpression of Viral Proteins and Involves Oxidative Radicals and Activation of IκB Kinase

Cited by 131 publications

References 51 publications

Reduced Expression of Nuclear Cyclic Adenosine 5′-Monophospate Response Element-Binding Proteins and IFN-γ Promoter Function in Disease Due to an Intracellular Pathogen

Reduced Expression of Nuclear Cyclic Adenosine 5′-Monophospate Response Element-Binding Proteins and IFN-γ Promoter Function in Disease Due to an Intracellular Pathogen

Influenza Virus-induced AP-1-dependent Gene Expression Requires Activation of the JNK Signaling Pathway

Essential Impact of NF-κB Signaling on the H5N1 Influenza A Virus-Induced Transcriptome

Contact Info

Product

Resources

About