Human Adenoviruses: Evading Detection by Cytotoxic T Lymphocytes

G.Eric Blair , Kersten T. Hall
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引用次数: 13

Abstract

Human adenoviruses cause lytic and persistent respiratory, enteric, and other infections. Adenoviruses can transform primary rodent cells and certain serotypes of human adenoviruses (such as adenovirus type 12 from subgenus A) induce tumors in newborn rodents. In both cases, adenovirus gene products mediate evasion of the cellular immune system by infected and tumor cells. In viral infection, a product of the early regionE3gene, a glycoprotein termed E3-19K, binds to and retains newly synthesised major histocompatibility complex (MHC) class I molecules in the endoplasmic reticulum thus rendering infected cells resistant to lysis by cytotoxic T lymphocytes. In addition, other products of theE3region confer on infected cells resistance to tumor necrosis factor-α-mediated lysis. Not all human adenovirus serotypes encode an E3-19K protein: viruses from subgenus A (such as adenovirus 12) and F (the enteric adenoviruses 40 and 41) do not encode an E3-19K molecule. In the case of Ad12, products of the viral E1A gene repress MHC class I heavy chain gene transcription. This leads to loss of MHC class I molecules from the surface of adenovirus 12-transformed cells and contributes to their evasion from cytotoxic T lymphocytes. Considerable progress has been made toward identifying the targets for E1A-mediated repression of the class I heavy chain promoter. In addition, adenovirus 12 mediates transcriptional repression of other genes in the MHC complex involved in antigen presentation, namely the transporter associated with antigen presentation (TAP) genes and MHC-encoded proteasome components, the low molecular weight proteins termed LMPs. Overall, adenoviruses display a variety of differing mechanisms for posttranslational (E3-19K) and transcriptional (E1A) repression of MHC class I expression that operate in all human viral serotypes studied, suggesting that evasion of cytotoxic T cell lysis forms an important part of the infection and oncogenic transformation strategies adopted by human adenoviruses.

人类腺病毒:逃避细胞毒性T淋巴细胞的检测
人类腺病毒引起溶解性和持续性呼吸道、肠道和其他感染。腺病毒可以转化啮齿动物的原代细胞,某些血清型的人腺病毒(如来自A亚属的12型腺病毒)在新生啮齿动物中诱导肿瘤。在这两种情况下,腺病毒基因产物介导感染细胞和肿瘤细胞逃避细胞免疫系统。在病毒感染中,早期区域基因的产物,一种称为E3-19K的糖蛋白,结合并保留内质网中新合成的主要组织相容性复合体(MHC) I类分子,从而使感染细胞抵抗细胞毒性T淋巴细胞的裂解。此外,e3区域的其他产物赋予感染细胞抵抗肿瘤坏死因子-α-介导的裂解的能力。并非所有人类腺病毒血清型都编码E3-19K蛋白:A亚属病毒(如腺病毒12)和F(肠道腺病毒40和41)不编码E3-19K分子。就Ad12而言,病毒E1A基因的产物抑制MHC I类重链基因的转录。这导致腺病毒12转化细胞表面MHC I类分子的丢失,并有助于它们逃避细胞毒性T淋巴细胞。在确定e1a介导的I类重链启动子抑制的靶标方面已经取得了相当大的进展。此外,腺病毒12介导MHC复合体中参与抗原呈递的其他基因的转录抑制,即与抗原呈递相关的转运蛋白(TAP)基因和MHC编码的蛋白酶体成分,即被称为LMPs的低分子量蛋白质。总的来说,腺病毒在翻译后(E3-19K)和转录(E1A)抑制MHC I类表达方面表现出多种不同的机制,这些机制在所有研究的人类病毒血清型中都起作用,这表明逃避细胞毒性T细胞裂解是人类腺病毒感染和致癌转化策略的重要组成部分。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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