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腺病毒转化细胞的致瘤性:腺病毒12的E1A区域赋予对自然杀伤细胞的抗性。

Tumorigenicity of adenovirus-transformed cells: region E1A of adenovirus 12 confers resistance to natural killer cells.

作者信息

Sawada Y, Föhring B, Shenk T E, Raska K

出版信息

Virology. 1985 Dec;147(2):413-21. doi: 10.1016/0042-6822(85)90143-6.

DOI:10.1016/0042-6822(85)90143-6
PMID:3878030
Abstract

Sensitivity of a library of rat cells transformed in vitro with viable recombinant adenoviruses to natural killer (NK) cells and allogeneic cytotoxic T cells has been studied and correlated with their oncogenic potential in syngeneic rats. All cell lines transformed with the sub370-12E1AB virus (containing E1A and E1B regions of Ad12) and with the sub370-12E1A virions (containing the E1A region of Ad12 and the E1B region of Ad5) showed a high degree of resistance to NK cells. The cell lines transformed with the sub370-12E1B virus (containing the E1A region of Ad5 and the E1B region of Ad12) were highly sensitive to NK cytotoxicity. While all cell lines transformed with virions containing the E1A genes of Ad5 expressed high levels of class I MHC antigen, only three of eight cell lines containing the E1A region of Ad12 showed detectable levels by flow cytometric analysis after staining with specific antibodies. All cell lines containing E1A genes of Ad5 were killed by in vitro generated allogeneic cytolytic T cells. Only three of eight cell lines containing the E1A region of Ad12 were killed by such CTLs; the level of cytotoxicity, however, did not reach that seen with the cells containing the E1A genes of Ad5. All cell lines containing the E1A and E1B genes of Ad12 were highly tumorigenic. Only two of four cell lines transformed with virus containing the E1A genes of Ad12 and E1B region of Ad5 were tumorigenic. The efficiency of tumor induction was low and the latent period was long confirming the importance of the E1B region. None of the cell lines transformed with virus containing the E1A region of Ad5 and the E1B genes of Ad12 were tumorigenic, reflecting their high degree of sensitivity to both natural and induced cellular immunity. Expression of the E1A region of Ad12 in transformed cells modulates not only the level of class I MHC antigens, but also confers resistance to NK cell cytotoxicity.

摘要

对用活的重组腺病毒体外转化的大鼠细胞文库对自然杀伤(NK)细胞和同种异体细胞毒性T细胞的敏感性进行了研究,并将其与它们在同基因大鼠中的致癌潜力相关联。所有用sub370 - 12E1AB病毒(包含Ad12的E1A和E1B区域)和sub370 - 12E1A病毒粒子(包含Ad12的E1A区域和Ad5的E1B区域)转化的细胞系对NK细胞表现出高度抗性。用sub370 - 12E1B病毒(包含Ad5的E1A区域和Ad12的E1B区域)转化的细胞系对NK细胞毒性高度敏感。虽然所有用包含Ad5的E1A基因的病毒粒子转化的细胞系都高水平表达I类MHC抗原,但在用特异性抗体染色后,通过流式细胞术分析,八个包含Ad12的E1A区域的细胞系中只有三个显示出可检测水平。所有包含Ad5的E1A基因的细胞系都被体外产生的同种异体溶细胞性T细胞杀死。八个包含Ad12的E1A区域的细胞系中只有三个被这种CTL杀死;然而,细胞毒性水平未达到包含Ad5的E1A基因的细胞系所观察到的水平。所有包含Ad12的E1A和E1B基因的细胞系都具有高度致瘤性。用包含Ad12的E1A基因和Ad5的E1B区域的病毒转化的四个细胞系中只有两个具有致瘤性。肿瘤诱导效率低且潜伏期长,证实了E1B区域的重要性。用包含Ad5的E1A区域和Ad12的E1B基因的病毒转化的细胞系均无致瘤性,这反映了它们对天然和诱导的细胞免疫的高度敏感性。Ad12的E1A区域在转化细胞中的表达不仅调节I类MHC抗原的水平,还赋予对NK细胞毒性的抗性。

相似文献

1
Tumorigenicity of adenovirus-transformed cells: region E1A of adenovirus 12 confers resistance to natural killer cells.腺病毒转化细胞的致瘤性:腺病毒12的E1A区域赋予对自然杀伤细胞的抗性。
Virology. 1985 Dec;147(2):413-21. doi: 10.1016/0042-6822(85)90143-6.
2
Region E1a of highly oncogenic adenovirus 12 in transformed cells protects against NK but not LAK cytolysis.在转化细胞中,高致癌性腺病毒12的E1a区域可抵御自然杀伤细胞(NK)的细胞溶解作用,但对淋巴因子激活的杀伤细胞(LAK)的细胞溶解作用无效。
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Identification of adenovirus E1A regions which affect MHC class I expression and susceptibility to cytotoxic T lymphocytes.鉴定影响主要组织相容性复合体I类分子表达及对细胞毒性T淋巴细胞敏感性的腺病毒E1A区域。
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Adenovirus type 5 and adenovirus type 12 recombinant viruses containing heterologous E1 genes are viable, transform rat cells, but are not tumorigenic in rats.含有异源E1基因的5型腺病毒和12型腺病毒重组病毒是有活力的,能转化大鼠细胞,但在大鼠中不具有致瘤性。
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Morphological transformation of human adenoviruses is determined to a large extent by gene products of region E1a.人类腺病毒的形态转化在很大程度上由E1a区的基因产物决定。
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Dependence of tumor-forming capacities of cells transformed by recombinants between adenovirus types 5 and 12 on expression of early region 1.5型腺病毒与12型腺病毒重组体转化细胞的致瘤能力对早期区域1表达的依赖性
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引用本文的文献

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Tumorigenic adenovirus 12 cells evade NK cell lysis by reducing the expression of NKG2D ligands.致瘤性腺病毒 12 细胞通过降低 NKG2D 配体的表达来逃避 NK 细胞溶解。
Immunol Lett. 2012 May 30;144(1-2):16-23. doi: 10.1016/j.imlet.2012.03.001. Epub 2012 Mar 14.
2
Macrophages kill human papillomavirus type 16 E6-expressing tumor cells by tumor necrosis factor alpha- and nitric oxide-dependent mechanisms.巨噬细胞通过肿瘤坏死因子α和一氧化氮依赖性机制杀死表达人乳头瘤病毒16型E6的肿瘤细胞。
J Virol. 2005 Jan;79(1):116-23. doi: 10.1128/JVI.79.1.116-123.2005.
3
Expression of an E1A/E7 chimeric protein sensitizes tumor cells to killing by activated macrophages but not NK cells.
E1A/E7嵌合蛋白的表达使肿瘤细胞对活化巨噬细胞的杀伤敏感,但对自然杀伤细胞不敏感。
J Virol. 2004 May;78(9):4646-54. doi: 10.1128/jvi.78.9.4646-4654.2004.
4
E1A and E1B proteins inhibit inflammation induced by adenovirus.E1A和E1B蛋白可抑制腺病毒诱导的炎症反应。
Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):3124-9. doi: 10.1073/pnas.0303709101. Epub 2004 Feb 19.
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Role of the E1A Rb-binding domain in repression of the NF-kappa B-dependent defense against tumor necrosis factor-alpha.E1A 与视网膜母细胞瘤结合结构域在抑制核因子-κB 介导的抗肿瘤坏死因子-α防御反应中的作用
Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):9966-71. doi: 10.1073/pnas.162082999. Epub 2002 Jul 15.
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Tumorigenicity of adenovirus-transformed rodent cells is influenced by at least two regions of adenovirus type 12 early region 1A.腺病毒12型早期区域1A的至少两个区域会影响腺病毒转化的啮齿动物细胞的致瘤性。
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7
Constructing chimeric type 12/type 5 adenovirus E1A genes and using them to identify an oncogenic determinant of adenovirus type 12.构建嵌合的12型/5型腺病毒E1A基因并利用它们鉴定12型腺病毒的致癌决定因素。
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Adenovirus 12-mediated down-regulation of the major histocompatibility complex (MHC) class I promoter: identification of a negative regulatory element responsive to Ad12 E1A.腺病毒12介导的主要组织相容性复合体(MHC)I类启动子下调:对Ad12 E1A有反应的负调控元件的鉴定。
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