Gene Induction Pathways Mediated by Distinct IRFs during Viral Infection

Nakaya, Takeo; Sato, Mitsuharu; Hata, Naoki; Asagiri, Masataka; Suemori, Hirofumi; Noguchi, Shigeru; Tanaka, Nobuyuki; Taniguchi, Tadatsugu

doi:10.1006/bbrc.2001.4913

Cited by 161 publications

(163 citation statements)

References 48 publications

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“…IRF-3 is constitutively expressed and activated post-translationally, whereas IRF-7 is regulated at the transcriptional level (reviewed by Nakaya et al, 2001). Servant et al (2001) recently demonstrated MV-induced IRF-3 activation, and in the present study we demonstrate MV-induced upregulation of the IRF-7 gene.…”

Section: Discussionsupporting

confidence: 77%

Measles virus-induced modulation of host-cell gene expression

Bolt¹,

Berg

Blixenkrone-Møller³

2002

Journal of General Virology

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The influence of measles virus (MV) infection on gene expression by human peripheral blood mononuclear cells (PBMCs) was examined with cDNA microarrays. The mRNA levels of more than 3000 cellular genes were compared between uninfected PBMCs and cells infected with either the Edmonston MV strain or a wild-type MV isolate. The MV-induced upregulation of individual genes identified by microarray analyses was confirmed by RT-PCR. In the present study, a total of 17 genes was found to be upregulated by MV infection. The Edmonston strain grew better in the PBMC cultures than the wild-type MV, and the Edmonston strain was a stronger inducer of the upregulated host cell genes than the wild-type virus. The anti-apoptotic B cell lymphoma 3 (Bcl-3) protein and the transcription factor NF-κB p52 subunit were upregulated in infected PBMCs both at the mRNA and at the protein level. Several genes of the interferon system including that for interferon regulatory factor 7 were upregulated by MV. The genes for a number of chaperones, transcription factors and other proteins of the endoplasmic reticulum stress response were also upregulated. These included the gene for the pro-apoptotic and growth arrest-inducing CHOP/GADD153 protein. Thus, the present study demonstrated the activation by MV of cellular mechanisms and pathways that may play a role in the pathogenesis of measles.

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Section: Discussionsupporting

confidence: 77%

Measles virus-induced modulation of host-cell gene expression

Bolt¹,

Berg

Blixenkrone-Møller³

2002

Journal of General Virology

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“…Those are: ISG15, ISG1-8, ISG56, ISG54, CXCL10, Viperin, NOXA, RANTES CXCL11, and USP18. [45][46][47][48] Induction of haptoglobin and antichymotrypsin ACT (SERPIN A3) by IKK⑀ can be presumably attributed to c/EBP␦ activation. 49,50 Some of the genes of the IKK⑀ transcriptome may be induced as secondary events through some transcription factors induced by IKK⑀.…”

Section: Resultsmentioning

confidence: 99%

The protein kinase IKKε can inhibit HCV expression independently of IFN and its own expression is downregulated in HCV-infected livers

et al. 2006

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H epatitis C virus (HCV) infection leads to the development of chronic hepatitis in 60% to 90% of infected individuals, cirrhosis in 0.5% to 30% of cases, and hepatocellular carcinoma at a rate of 1% to 3% per year. 1 The current approved treatment for HCV infection is pegylated interferon alpha (IFN-␣) in combination with ribavirin. This leads to clearance of the virus in 50% to 80% of cases, depending on the infecting HCV genotype. In particular, HCV of genotype 1 is the most resistant to IFN treatment. 2 HCV can interfere with the response of cells to IFN, through its viral proteins targeting either the IFN-activated JAK/STAT signaling pathway 3-5 or through other processes, leading to inhibition of action of the IFN-induced antiviral proteins. 6 In addition to this, HCV interferes with IFN induction, and more generally, with the induction of the innate immune response. The innate immune response is triggered in response to a variety of pathogens, such as bacteria and viruses, and is essential for a rapid limitation in the spread or action of these pathogens. IFN induction can take place after interaction of extracellular nucleic acids to members of the Toll-like receptor family 7-10 and after viral intrusion in the cytoplasm through the interaction of viral double-stranded RNAs (dsRNAs) with specific RNA helicases, such as RIG-I 11 or MDA-5. 12 For instance, the From the

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“…45,46 The stimuli remain to be defined; however, IFN-a was reported expressing at low levels in normal or axenic mice. 47 Rapid stimulation of the Tolllike receptor causes IRF3 activation, IFN-b synthesis and signal transduction through the type I IFNAR.…”

Section: Discussionmentioning

confidence: 99%

Genomic view of IFN-α response in pre-autoimmune NZB/W and MRL/lpr mice

Shen

et al. 2007

Genes Immun

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Interferon (IFN)-a is involved in the pathogenesis of systemic lupus erythematosus. Studies in murine lupus models have revealed that type I IFN exerts either a protective effect in MRL/lpr, or can detrimentally impact disease progression, as in NZB/ W mice. To understand this paradox, we examined the kinetic global gene expression in pre-autoimmune NZB/W-, MRL/lprand normal BALB/c-derived splenic mononuclear cells following ex vivo IFN-a treatment. Analysis of IFN-a-induced gene expression patterns revealed genes associated with antiproliferative activity of IFN-a including CDKN1A, GADD45B, pituitary tumor-transforming 1, SCOTIN, ataxia telangiectasia-mutated homolog and calcyclin-binding protein were upregulated in MRL/ lpr and/or BALB/c mice. Of IFN-a-induced genes differentially expressed in NZB/W vs BALB/c and MRL/lpr mice at 3 h time point, enhanced expression of CCND1, cyclin D2, matrix metalloproteinase 13 and a panel of cytokines and chemokines and impaired expression of negative inflammatory regulators CD69 and an Src family kinase hemopoietic cell kinase were notable. Interestingly, the splenic mononuclear cells from the NZB/W not MRL/lpr lupus-prone mice at the pre-autoimmune stage before ex vivo IFN-a treatment, have increased expression of many known IFN-regulated genes. These results provide a unique genomic view of ex vivo IFN-a response in two lupus-prone models, and help to have an insight into the role of IFN-a in lupus pathogenesis Genes and Immunity (2007) IntroductionSystemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease characterized by a break of immune tolerance to self antigens, resulting in inflammation and damage to a range of organ systems. The exact pathoetiology of SLE remains elusive. Elevated serum levels of IFN-a have long been observed and correlated with disease activity. A series of studies using microarray gene expression analysis in patient peripheral blood cells demonstrated an 'IFN signature' in SLE, which correlated with renal and hematological involvement of phenotypes. [1][2][3][4][5][6] Supporting evidence has also come from studies on murine lupus. The (New Zealand Black (NZB) Â New Zealand White (NZW))F1 hybrid female mice (NZB/W) develop a disease closely resembling human SLE, characterized by the production of antinuclear antibodies, severe glomerulonephritis and early mortality. In the NZB parental strain, which also develops a lupus-like syndrome, homozygous IFN-a/b R-deleted NZB mice had significantly reduced antierythrocyte autoantibodies, erythroblastosis, hemolytic anemia, anti-DNA autoantibodies, kidney disease and mortality. 7 In contrast to normal BALB/c mice, continuous in vivo treatment of IFN-a in pre-autoimmune NZB/W mice from 8 weeks of age precipitates the autoimmune process and kidney damage, leading to premature death from severe immune complex glomerulonephritis. This result provides a direct evidence that IFN-a is implicated in the pathogenesis of SLE. 8 Thus, the type I IFNs have emerged as a dominant target in the path...

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Gene Induction Pathways Mediated by Distinct IRFs during Viral Infection

Cited by 161 publications

References 48 publications

Measles virus-induced modulation of host-cell gene expression

Measles virus-induced modulation of host-cell gene expression

The protein kinase IKKε can inhibit HCV expression independently of IFN and its own expression is downregulated in HCV-infected livers

Genomic view of IFN-α response in pre-autoimmune NZB/W and MRL/lpr mice

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