國家衛生研究院 NHRI:Item 3990099045/2120
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    题名: Epstein-Barr virus latent membrane protein-1 mediates upregulation of tumor necrosis factor-alpha in EBV-infected T cells: Implications for the pathogenesis of hemophagocytic syndrome
    作者: Lay, JD;Chuang, SE;Rowe, M;Su, IJ
    贡献者: Division of Clinical Research;National Institute of Cancer Research
    摘要: The infection of human T cells by Epstein-Barr virus (EBV) may result in a fatal hemophagocytic syndrome (HS). We have previously shown that EBV can selectively upregulate the tumor necrosis factor-alpha (TNFalpha) gene and lead to activation of macrophages in a manner similar to the pathobiology of HS in EBV-infected T lymphoproliferative disorders (LPDs). This study was designed to further clarify the specific EBV gene product(s) responsible for TNFalpha upregulation. RT-PCR analysis of EBV gene expression was performed on 2 CR2-transfected EBV-infected T lymphoma lines and 2 EBV-infected B cell lines. To identify the EBV gene responsible for upregulation of TNFalpha, 2 reporter recombinant plasmids, pTNFalpha-CAT and pTNFalpha-Luc, were then constructed and co-transfected with the expression plasmids of the EBV latent and lytic genes (EBNA-1, EBNA-2, LMP-1, LMP-2A, and BZLF-1) in both T and B cell lines. Analyses using ELISA and Western blotting were further performed to detect the secreted TNFalpha. The results revealed that EBNA-1 and LMP-1 were consistently expressed in EBV-infected T cell lines (type II latency), while a type III latency with expression of EBNA-1, EBNA-2, LMP-1, and lytic BZLF transcripts was detected in EBV-infected B cell lines. LMP-1 was demonstrated to be the only EBV gene product to transactivate the TNFalpha gene, and this phenomenon was observed only in T, not in B, cells. Enhanced secretion of TNF-alpha protein was also detected in LMP1-transfected T cell lines. We concluded that LMP1 is the candidate protein in the upregulation of the TNFalpha gene in T cells and is probably responsible for the pathogenesis of HS in EBV-infected T lymphoproliferative disorders.
    关键词: Medicine, Research & Experimental
    日期: 2003-01
    關聯: Journal of Biomedical Science. 2003 Jan;10(1):146-155.
    Link to: http://dx.doi.org/10.1007/BF02256006
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1021-7770&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000181460500015
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=0037261728
    显示于类别:[蘇益仁(2002-2015)] 期刊論文
    [莊雙恩] 期刊論文

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