In vivo expression profile of the antiviral restriction factor and tumor-targeting antigen CD317/BST-2/HM1.24/tetherin in humans
In vivo expression profile of the antiviral restriction factor and tumor-targeting antigen CD317/BST-2/HM1.24/tetherin in humans
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DOI：
10.1073/pnas.1101684108
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发表时间：
2011-08-16
影响因子：
11.1
通讯作者：
Keppler, Oliver T.
中科院分区：
文献类型：
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作者：
Erikson, Elina;Adam, Tarek;Keppler, Oliver T.
人类 CD317 是一种内在免疫因子，可限制培养物中受感染细胞释放包膜病毒，包括主要病原体 HIV 和拉沙病毒。它对于人类感染控制的重要性尚不清楚，部分原因是其体内表达模式的定义不完全。 CD317 也被提议作为多发性骨髓瘤免疫治疗的选择性靶标。为了为 CD317 的生物学功能、调节和治疗潜力的研究提供框架，我们对来自 210 多名患者的 25 个健康器官的 468 个组织样本进行了基于微阵列的表达谱分析。我们发现CD317蛋白在所有测试的器官中都有不同程度的表达，并在许多特殊的细胞类型中检测到，包括肝细胞、肺细胞、大唾液腺导管、胰腺和肾脏、潘氏细胞、上皮细胞、Leydig细胞、浆细胞、骨髓基质细胞、单核细胞和血管内皮。尽管许多这些细胞类型是病原性病毒的体内靶标，但仅在其中一些细胞中记录了 CD317 或病毒编码拮抗剂的限制。 CD317 与 IFN 生物标志物 MxA 在体内的有限细胞类型依赖性共表达以及器官外植体中缺乏反应性刺激表明干扰素可能仅部分调节 CD317。这种体内表达谱揭示了 CD317 的生物学和物种特异性，识别了病毒与该限制因子的多个迄今为止未知的相互作用位点，并反驳了其限制性组成型表达和初级 IFN 诱导性的概念。 CD317 的广泛表达使其作为免疫治疗靶点的适用性受到质疑。
Human CD317 is an intrinsic immunity factor that restricts the release of enveloped viruses, including the major pathogens HIV and Lassa virus, from infected cells in culture. Its importance for infection control in humans is unclear, due in part to its incompletely defined in vivo expression pattern. CD317 also has been proposed as a selective target for immunotherapy of multiple myeloma. To provide a framework for studies of the biological functions, regulation, and therapeutic potential of CD317, we performed microarray-based expression profiling in 468 tissue samples from 25 healthy organs from more than 210 patients. We found that CD317 protein was expressed to varying degrees in all organs tested and detected in a number of specialized cell types, including hepatocytes, pneumocytes, ducts of major salivary glands, pancreas and kidney, Paneth cells, epithelia, Leydig cells, plasma cells, bone marrow stromal cells, monocytes, and vascular endothelium. Although many of these cell types are in vivo targets for pathogenic viruses, restriction by CD317 or virus-encoded antagonists has been documented in only some of them. Limited cell type-dependent coexpression of CD317 with the IFN biomarker MxA in vivo and lack of responsive stimulation in organ explants suggest that interferons may only partially regulate CD317. This in vivo expression profiling sheds light on the biology and species-specificity of CD317, identifies multiple thus far unknown interaction sites of viruses with this restriction factor, and refutes the concept of its restricted constitutive expression and primary IFN inducibility. CD317's widespread expression calls into question its suitability as a target for immunotherapy.