Interferon regulatory factor 7 is involved in the growth of Epstein–Barr virus-transformed human B lymphocytes

Xu, Dongsheng; Zhang, Yanyan; Zhao, Lingjun; Cao, Ming; Lingel, Amy; Zhang, Luwen

doi:10.1016/j.virusres.2014.09.005

Cited by 6 publications

(4 citation statements)

References 53 publications

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“…Although neurons do not produce IFN in response to alphavirus infection in vitro, the expression of functionally mature IRF7 increases with neuronal maturation [88]. Knock down of IRF7 expression in EBV-transformed B cells increases apoptosis, so IRF7 deficiency may increase the likelihood of SINV-induced neuronal cell death [89]. IRF7 deficiency may also increase susceptibility to neurotoxic factors such as TNFa produced by glial cells or inflammatory cells infiltrating the CNS from the periphery.…”

Section: Irf3à/à Mice Develop Fatal Disease After Infection With Wnvmentioning

confidence: 99%

Interferon regulatory factors 3 and 7 have distinct roles in the pathogenesis of alphavirus encephalomyelitis

Schultz

Troisi

Baxter

et al. 2019

Journal of General Virology

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Interferon (IFN) regulatory factors (IRFs) are important determinants of the innate response to infection. We evaluated the role(s) of combined and individual IRF deficiencies in the outcome of infection of C57BL/6 mice with Sindbis virus, an alphavirus that infects neurons and causes encephalomyelitis. The brain and spinal cord levels of Irf7, but not Irf3 mRNAs, were increased after infection. IRF3/5/7À/À and IRF3/7À/À mice died within 3-4 days with uncontrolled virus replication, similar to IFNa receptordeficient mice, while all wild-type (WT) mice recovered. IRF3À/À and IRF7À/À mice had brain levels of IFNa that were lower, but brain and spinal cord levels of IFNb and IFN-stimulated gene mRNAs that were similar to or higher than WT mice without detectable serum IFN or increases in Ifna or Ifnb mRNAs in the lymph nodes, indicating that the differences in outcome were not due to deficiencies in the central nervous system (CNS) type I IFN response. IRF3À/À mice developed persistent neurological deficits and had more spinal cord inflammation and higher CNS levels of Il1b and Ifng mRNAs than WT mice, but all mice survived. IRF7À/À mice died 5-8 days after infection with rapidly progressive paralysis and differed from both WT and IRF3À/À mice in the induction of higher CNS levels of IFNb, tumour necrosis factor (TNF) a and Cxcl13 mRNA, delayed virus clearance and more extensive cell death. Therefore, fatal disease in IRF7À/À mice is likely due to immune-mediated neurotoxicity associated with failure to regulate the production of inflammatory cytokines such as TNFa in the CNS.

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Section: Irf3à/à Mice Develop Fatal Disease After Infection With Wnvmentioning

confidence: 99%

Interferon regulatory factors 3 and 7 have distinct roles in the pathogenesis of alphavirus encephalomyelitis

Schultz

Troisi

Baxter

et al. 2019

Journal of General Virology

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“…The results showed that knock-down of IRF-7 ( Figure 4) expression reduced LMP1 mRNA level in the cell line and LMP1 protein level around new blood vessel of tumor tissue, respectively. These results could be explained based on findings from the previous studies, in which LMP1 could influence tumor development from various aspects, including angiogenesis, invasion, metastasis, apoptosis, as well as proliferation [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]. Therefore, down-regulation of LMP1 may be one of the mechanisms in siIRF-7-induced tumor growth suppression of NPC in vivo.…”

Section: Knock-down Of Irf-7 Down-regulated Lmp1 Expression In Vitro ...mentioning

confidence: 88%

“…The absorbance at a wavelength of 490 nm was recorded using a 96-well plate reader. There was no dramatic changes in cell number within the time frame, and procedures were described in a previous study [8].…”

Section: Cell Proliferation and Mtt Assaymentioning

confidence: 89%

“…However, the relationship between LMP1 and IRFs in oncogenesis is unclear. IRF-7 is one of nine members of the interferon regulatory factor (IRF) proteins family, which was originally identified as transcriptional regulators of the type I interferon system, and the IRF proteins family has multiple functions that includes reproduction, development, stress responses, immune defense, and carcinogenesis [7][8][9]. To note, IRF-7 was cloned in the context of EBV latency.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

EBV LMP1 regulates cancer growth through IRF-7 in nasopharyngeal carcinoma.

Wu¹,

Xu²,

Qian³

et al. 2017

molecular-oncology

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The cellular Interferon (IFN) regulatory factor-7 (IRF-7) was originally identified in cells with Epstein-Barr virus (EBV) infection, which constituted of positive circuit with viral oncoprotein latent membrane protein 1 (LMP1), and both proteins are involved in neoplasia. EBV is known to be associated with the development of various cancers, including Hodgkin lymphoma, non-Hodgkin lymphoma (NHL), Burkitt lymphoma, gastric lymphoma, and nasopharyngeal carcinoma (NPC). Although the exact role of IRF-7 in EBV-related oncogenesis is not clear, in this study, we demonstrated the role of IRF-7 in angiogenesis suppression via LMP1 down-regulation. Additionally, we employed knock-down of IRF-7 and verified the inhibition of IRF-7 in NPC growth in vivo. These findings suggest that IRF-7 could be a potential therapeutic target in EBV-infected NPC tumors.

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The Latent Membrane Protein 1 (LMP1)

Kieser

Sterz

2015

Current Topics in Microbiology and Immunology

123

127

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Almost exactly twenty years after the discovery of Epstein-Barr virus (EBV), the latent membrane protein 1 (LMP1) entered the EBV stage, and soon thereafter, it was recognized as the primary transforming gene product of the virus. LMP1 is expressed in most EBV-associated lymphoproliferative diseases and malignancies, and it critically contributes to pathogenesis and disease phenotypes. Thirty years of LMP1 research revealed its high potential as a deregulator of cellular signal transduction pathways leading to target cell proliferation and the simultaneous subversion of cell death programs. However, LMP1 has multiple roles beyond cell transformation and immortalization, ranging from cytokine and chemokine induction, immune modulation, the global alteration of gene and microRNA expression patterns to the regulation of tumor angiogenesis, cell-cell contact, cell migration, and invasive growth of tumor cells. By acting like a constitutively active receptor, LMP1 recruits cellular signaling molecules associated with tumor necrosis factor receptors such as tumor necrosis factor receptor-associated factor (TRAF) proteins and TRADD to mimic signals of the costimulatory CD40 receptor in the EBV-infected B lymphocyte. LMP1 activates NF-κB, mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3-K), IRF7, and STAT pathways. Here, we review LMP1's molecular and biological functions, highlighting the interface between LMP1 and the cellular signal transduction network as an important factor of virus-host interaction and a potential therapeutic target.

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Interferon regulatory factor 7 is involved in the growth of Epstein–Barr virus-transformed human B lymphocytes

Cited by 6 publications

References 53 publications

Interferon regulatory factors 3 and 7 have distinct roles in the pathogenesis of alphavirus encephalomyelitis

Interferon regulatory factors 3 and 7 have distinct roles in the pathogenesis of alphavirus encephalomyelitis

EBV LMP1 regulates cancer growth through IRF-7 in nasopharyngeal carcinoma.

The Latent Membrane Protein 1 (LMP1)

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