Cytomegalovirus selectively blocks antigen processing and presentation of its immediate-early gene product
Cytomegalovirus selectively blocks antigen processing and presentation of its immediate-early gene product
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DOI：
10.1038/383720a0
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发表时间：
1996-10-24
期刊：
影响因子：
64.8
通讯作者：
Greenberg, PD
中科院分区：
文献类型：
--
作者：
Gilbert, MJ;Riddell, SR;Greenberg, PD
CD 8（+）细胞毒性T淋巴细胞识别病毒感染的细胞需要将病毒蛋白加工成肽，衍生肽转运到内质网并插入主要组织相容性复合物I类分子的结合沟中，抗原复合物输出到细胞表面（1）。然而，病毒病原体可以破坏这一过程并干扰免疫识别（1-4）。这些机制对于大型病毒如人巨细胞病毒（CMV）可能是至关重要的，尽管在病毒基因表达的连续立即早期、早期和晚期阶段期间产生超过200种潜在抗原性蛋白，但CMV引起持续感染（5，6）。CMV早期基因表达的产物可以全面阻断I类呈递（7-10）并防止细胞毒性T淋巴细胞识别感染的细胞，但是一种必需的病毒转录因子，即72 K主要的立即早期蛋白，在这种阻断之前大量表达。然而，在血清阳性个体中仅存在少数宿主CD 8（+）细胞毒性T淋巴细胞，其对立即早期蛋白具有特异性，并且这些细胞裂解CMV感染的细胞的能力很差（11）。在这里，我们证明了具有相关激酶活性的CMV基质蛋白可以选择性地废除立即早期肽的递呈，并表明病毒蛋白的修饰可能会导致限制对加工机制的访问并逃避细胞毒性T细胞的识别。
RECOGNITION of virus-infected cells by CD8(+) cytotoxic T lymphocytes requires that the viral proteins be processed into peptides, the derived peptides transported into the endoplasmic reticulum and inserted into the binding groove of a major histocompatability complex class I molecule, and the antigenic complex exported to the cell surface(1). However, viral pathogens can disrupt this process and interfere with immune recognition(1-4). These mechanisms may be vital to large viruses such as human cytomegalovirus (CMV), which causes persistent infection despite producing over 200 potentially antigenic proteins during the sequential immediate-early, early and late phases of viral gene expression(5,6). Products of CMV early-phase gene expression can globally block class I presentation(7-10) and prevent recognition of infected cells by cytotoxic T lymphocytes, but an essential viral transcription factor, the 72K principal immediate-early protein, is abundantly expressed before this blockade. However, only a few host CD8(+) cytotoxic T lymphocytes specific for immediate-early protein are present in seropositive individuals, and these lyse CMV-infected cells poorly(11). Here we demonstrate selective abrogation of immediate-early peptide presentation by a CMV matrix protein with associated kinase activity and suggest that modification of a viral protein can result in limiting access to the processing machinery and evasion of cytotoxic-T-cell recognition.