Myxoma virus leukemia-associated protein is responsible for major histocompatibility complex class I and Fas-CD95 down-regulation and defines scrapins, a new group of surface cellular receptor abductor proteins
Myxoma virus leukemia-associated protein is responsible for major histocompatibility complex class I and Fas-CD95 down-regulation and defines scrapins, a new group of surface cellular receptor abductor proteins
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DOI：
10.1128/jvi.76.6.2912-2923.2002
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发表时间：
2002-03-01
影响因子：
5.4
通讯作者：
Messud-Petit, F
中科院分区：
文献类型：
--
作者：
Guerin, JL;Gelfi, J;Messud-Petit, F
下调主要组织相容性I类（MHC-I）分子是病毒在宿主体内生存的一种策略。黏液瘤病毒是引起兔黏液瘤病的痘病毒科的一员，它可以下调mhc - 1分子的表达，但病毒因子尚未被描述。我们克隆并鉴定了一个编码内质网（ER）蛋白的基因，该蛋白含有一个非典型锌指和两个跨膜结构域，我们称之为黏液瘤病毒白血病相关蛋白（MV-LAP）。转染后，MV-LAP下调表面MHC-I和Fas-CD95分子；其机制可能涉及内吞作用的加剧，并在内质网保留信号被移除时丢失。此外，mhc -1限制性抗原特异性细胞溶解T淋巴细胞（CTL）对黏液瘤病毒感染的抗原呈递靶细胞的裂解活性显著降低，表明MV-LAP下调mhc -1与体外杀伤CTL之间存在很强的相关性。用敲除病毒进行的体内实验表明，MV-LAP是一种毒力因子，可能参与了粘液瘤病的免疫抑制特征。数据库分析显示MV-LAP在疱疹病毒和其他痘病毒中有同源物。我们提出命名“刮擦蛋白”来定义一组新的er驻留表面细胞受体外展蛋白。刮屑蛋白对细胞表面分子的下调可能有助于在病毒感染期间保护被感染的细胞。
Down-modulation of major histocompatibility class I (MHC-I) molecules is a viral strategy for survival in the host. Myxoma virus, a member of the Poxviridae family responsible for rabbit myxomatosis, can down-modulate the expression of MHC-I molecules, but the viral factor(s) has not been described. We cloned and characterized a gene coding for an endoplasmic reticulum (ER)-resident protein containing an atypical zinc finger and two transmembrane domains, which we called myxoma virus leukemia-associated protein (MV-LAP). MV-LAP down-regulated surface MHC-I and Fas-CD95 molecules upon transfection; the mechanism probably involves an exacerbation of endocytosis and was lost when the ER retention signal was removed. In addition, the lytic activity of MHC-1-restricted antigen-specific cytolytic T lymphocytes (CTL) against myxoma virus-infected antigen-presenting target cells was significantly reduced, revealing a strong correlation between MHC-I down-regulation by MV-LAP and CTL killing in vitro. In vivo experiments with a knockout virus showed that MV-LAP is a virulence factor, potentially involved in the immunosuppression characteristic of myxomatosis. Data bank analysis revealed that MV-LAP has homologs in herpesviruses and other poxviruses. We propose the name "scrapins" to define a new group of ER-resident surface cellular receptor abductor proteins. The down-regulation of cell surface molecules by scrapins probably helps protect infected cells during viral infections.