NKG2D-mediated natural killer cell protection against cytomegalovirus is impaired by viral gp40 modulation of retinoic acid early inducible 1 gene molecules.
NKG2D-mediated natural killer cell protection against cytomegalovirus is impaired by viral gp40 modulation of retinoic acid early inducible 1 gene molecules.
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DOI：
10.1084/jem.20021973
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发表时间：
2003-05-19
期刊：
影响因子：
--
通讯作者：
Lanier LL
中科院分区：
文献类型：
--
作者：
Lodoen M;Ogasawara K;Hamerman JA;Arase H;Houchins JP;Mocarski ES;Lanier LL
自然杀伤（NK）细胞在针对巨细胞病毒（CMV）感染的先天免疫应答中起关键作用。尽管CMV编码几种致力于逃避适应性免疫的基因产物，但病毒对NK细胞活性的调节才刚刚开始被认识。先前的研究表明，小鼠CMV m152编码的gp 40糖蛋白减少了病毒感染细胞表面活化NK细胞受体NKG 2D的配体表达。在这里，我们已经定义了受影响的精确配体，并在体外和体内对CMV感染的免疫应答中直接涉及NKG 2D。小鼠CMV（MCMV）感染可有效诱导所有五种已知的视黄酸早期诱导1（RAE-1）基因（RAE-1α、RAE-1β、RAE-1δ、RAE-1 β和RAE-1γ）的转录，但不诱导H-60。gp 40特异性下调所有RAE-1蛋白的细胞表面表达，但不下调H-60，并减少NK细胞对CMV感染细胞的干扰素γ产生。与先前的发现一致，m152缺失突变病毒（Δm152）在体内的毒力低于MCMV野生型Smith株。感染前用中和抗NKG 2D抗体处理BALB/c小鼠，可使脾脏和肝脏中Δm152病毒滴度增加至野生型病毒水平。这些实验表明，gp 40通过破坏RAE-1-NKG 2D相互作用来损害病毒感染细胞的NK细胞识别。
Natural killer (NK) cells play a critical role in the innate immune response against cytomegalovirus (CMV) infections. Although CMV encodes several gene products committed to evasion of adaptive immunity, viral modulation of NK cell activity is only beginning to be appreciated. A previous study demonstrated that the mouse CMV m152-encoded gp40 glycoprotein diminished expression of ligands for the activating NK cell receptor NKG2D on the surface of virus-infected cells. Here we have defined the precise ligands that are affected and have directly implicated NKG2D in immune responses to CMV infection in vitro and in vivo. Murine CMV (MCMV) infection potently induced transcription of all five known retinoic acid early inducible 1 (RAE-1) genes (RAE-1α, RAE-1β, RAE-1δ, RAE-1ɛ, and RAE-1γ), but not H-60. gp40 specifically down-regulated the cell surface expression of all RAE-1 proteins, but not H-60, and diminished NK cell interferon γ production against CMV-infected cells. Consistent with previous findings, a m152 deletion mutant virus (Δm152) was less virulent in vivo than the wild-type Smith strain of MCMV. Treatment of BALB/c mice with a neutralizing anti-NKG2D antibody before infection increased titers of Δm152 virus in the spleen and liver to levels seen with wild-type virus. These experiments demonstrate that gp40 impairs NK cell recognition of virus-infected cells through disrupting the RAE-1–NKG2D interaction.
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影响因子：
11.4
作者：
Kleijnen, MF;Huppa, JB;Ploegh, HL
通讯作者：
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影响因子：
32.4
作者：
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作者：
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DOI：
10.1084/jem.162.6.1745
发表时间：
1985-12-01
期刊：
The Journal of experimental medicine
影响因子：
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作者：
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通讯作者：
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作者：
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