Distribution of cellular HSV-1 receptor expression in human brain.
Distribution of cellular HSV-1 receptor expression in human brain.
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DOI：
10.1007/s13365-016-0504-x
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发表时间：
2017-06
影响因子：
3.2
通讯作者：
Haas JG
中科院分区：
文献类型：
--
作者：
Lathe R;Haas JG
单纯疱疹病毒1型（HSV-1）是一种嗜神经病毒，与影响大脑不同区域的一系列急性和慢性神经系统疾病有关。不寻常的是，HSV-1进入细胞需要病毒蛋白糖蛋白D（gD）和糖蛋白B（gB）与不同的细胞受体蛋白相互作用。已经鉴定了几种不同的gD和gB受体，包括作为gD受体的TNFRSF 14/HVEM和PVRL 1/nectin 1以及作为gB受体的PILRA、MAG和MYH 9。我们使用在线转录组数据库研究了这些受体分子在成人和发育中的人脑不同区域的表达。尽管所有HSV-1受体在不同的脑区显示出不同的表达模式，但Allan Brain Atlas（阿坝）报告海马中gD和gB受体的表达增加。具体而言，对于PVRL 1、TNFRFS 14和MYH 9，海马表达的差异z评分（表达增加的相对水平的量度）分别上升至2.9、2.9和2.5，与典型的富含海马的盐皮质激素受体（NR 3C 2，z = 3.1）的z评分相当。这些数据在人脑转录组（HBT）数据库中得到证实，但HBT数据表明MAG表达也在海马中富集。HBT数据库允许的发展模式的表达进行调查，我们报告说，所有HSV 1受体显着增加妊娠期和出生后/成人期之间的表达水平。这些结果表明，成人海马中几种HSV-1 gD和gB受体的差异受体表达水平可能是该脑区对HSV-1感染的易感性的基础。
Herpes simplex virus type 1 (HSV-1) is a neurotropic virus linked to a range of acute and chronic neurological disorders affecting distinct regions of the brain. Unusually, HSV-1 entry into cells requires the interaction of viral proteins glycoprotein D (gD) and glycoprotein B (gB) with distinct cellular receptor proteins. Several different gD and gB receptors have been identified, including TNFRSF14/HVEM and PVRL1/nectin 1 as gD receptors and PILRA, MAG, and MYH9 as gB receptors. We investigated the expression of these receptor molecules in different areas of the adult and developing human brain using online transcriptome databases. Whereas all HSV-1 receptors showed distinct expression patterns in different brain areas, the Allan Brain Atlas (ABA) reported increased expression of both gD and gB receptors in the hippocampus. Specifically, for PVRL1, TNFRFS14, and MYH9, the differential z scores for hippocampal expression, a measure of relative levels of increased expression, rose to 2.9, 2.9, and 2.5, respectively, comparable to the z score for the archetypical hippocampus-enriched mineralocorticoid receptor (NR3C2, z = 3.1). These data were confirmed at the Human Brain Transcriptome (HBT) database, but HBT data indicate that MAG expression is also enriched in hippocampus. The HBT database allowed the developmental pattern of expression to be investigated; we report that all HSV1 receptors markedly increase in expression levels between gestation and the postnatal/adult periods. These results suggest that differential receptor expression levels of several HSV-1 gD and gB receptors in the adult hippocampus are likely to underlie the susceptibility of this brain region to HSV-1 infection.