Comparative RNAi screening reveals host factors involved in enterovirus infection of polarized endothelial monolayers.
Comparative RNAi screening reveals host factors involved in enterovirus infection of polarized endothelial monolayers.
复制标题
DOI：
10.1016/j.chom.2011.01.001
复制
发表时间：
2011-01-20
影响因子：
30.3
通讯作者：
Cherry S
中科院分区：
文献类型：
--
作者：
Coyne CB;Bozym R;Morosky SA;Hanna SL;Mukherjee A;Tudor M;Kim KS;Cherry S
肠道病毒，包括柯萨奇病毒B（CVB）和脊髓灰质炎病毒（PV），可以通过血脑屏障（BB B）内皮进入中枢神经系统，引起无菌性脑膜炎。为了鉴定CVB和PV感染人脑微血管内皮细胞（一种体外BBB模型）所需的细胞组分，我们进行了比较性RNAi筛选，并鉴定了117个影响感染的基因。而大部分的基因，其耗尽增强感染（17 22）广泛抗肠道病毒，只有46的95个基因的耗尽抑制感染所需的CVB和PV，包括细胞信号通路的组件，如腺苷酸环化酶。下调的基因包括Rab GTP酶，Src酪氨酸激酶和酪氨酸磷酸酶，显示其对CVB或PV感染的需求的特异性。这些发现强调了肠道病毒在BBB内皮细胞中进入和复制的途径，BBB内皮细胞是这些病毒的一种特殊的临床相关细胞类型。
Enteroviruses, including coxsackievirus B (CVB) and poliovirus (PV), can access the CNS through the blood brain barrier (BBB) endothelium to cause aseptic meningitis. To identify cellular components required for CVB and PV infection of human brain microvascular endothelial cells, an in vitro BBB model, we performed comparative RNAi screens and identified 117 genes that influenced infection. Whereas a large proportion of genes whose depletion enhanced infection (17 of 22) were broadly anti-enteroviral, only 46 of the 95 genes whose depletion inhibited infection were required by both CVB and PV and included components of cell signaling pathways such as adenylate cyclases. Downregulation of genes including Rab GTPases, Src tyrosine kinases, and tyrosine phosphatases, displayed specificity in their requirement for either CVB or PV infection. These findings highlight the pathways hijacked by enteroviruses for entry and replication in the BBB endothelium, a specialized and clinically relevant cell type for these viruses.