Wild-type Measles Virus Infection Upregulates Poliovirus Receptor-Related 4 and Causes Apoptosis in Brain Endothelial Cells by Induction of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand
Wild-type Measles Virus Infection Upregulates Poliovirus Receptor-Related 4 and Causes Apoptosis in Brain Endothelial Cells by Induction of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand
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DOI：
10.1097/nen.0b013e31829a26b6
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发表时间：
2013-07-01
影响因子：
3.2
通讯作者：
Cosby, Sara Louise
中科院分区：
文献类型：
--
作者：
Abdullah, Hani'ah;Brankin, Brenda;Cosby, Sara Louise
患有麻疹病毒（MV）感染神经系统并发症的儿童中，少量脑内皮细胞（BEC）受到感染。这可能为病毒进入中枢神经系统提供了一种机制，但具体机制尚不清楚。需要体外培养系统和动物模型来阐明内皮事件。我们比较了野生型 (WT)、疫苗和啮齿动物适应型 MV 毒株感染、复制和诱导人和鼠脑内皮细胞（分别为 HBEC 和 MBEC）细胞凋亡的能力。小鼠脑内也受到感染。所有 MV 染色剂均有效感染 HBEC 并诱导 MV 受体 PVRL4。 MBEC 中也发生了有效的 WT MV 产生。在 HBEC 和 MBEC 中观察到与激活的 caspase 3 染色相关的广泛单层破坏，其中 WT MV 最为明显。 MV 感染诱导肿瘤坏死因子相关凋亡诱导配体 (TRAIL)，而非 Fas 配体。用抗 TRAIL 抗体处理来自 MV 感染的 MBEC 培养物的上清液，可阻断 caspase 3 的表达和单层破坏。 TRAIL 也在受感染小鼠大脑的内皮细胞和其他细胞类型中表达。这是首次证明用 WT MV 感染少量 BEC 可以实现高效病毒生产、诱导 TRAIL 以及随后广泛的细胞凋亡。
Small numbers of brain endothelial cells (BECs) are infected in children with neurologic complications of measles virus (MV) infection. This may provide a mechanism for virus entry into the central nervous system, but the mechanisms are unclear. Both in vitro culture systems and animal models are required to elucidate events in the endothelium. We compared the ability of wild-type (WT), vaccine, and rodent-adapted MV strains to infect, replicate, and induce apoptosis in human and murine brain endothelial cells (HBECs and MBECs, respectively). Mice also were infected intracerebrally. All MV stains productively infected HBECs and induced the MV receptor PVRL4. Efficient WT MV production also occurred in MBECs. Extensive monolayer destruction associated with activated caspase 3 staining was observed in HBECs and MBECs, most markedly with WT MV. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), but not Fas ligand, was induced by MV infection. Treatment of MBECs with supernatants from MV-infected MBEC cultures with an anti-TRAIL antibody blocked caspase 3 expression and monolayer destruction. TRAIL was also expressed in the endothelium and other cell types in infected murine brains. This is the first demonstration that infection of low numbers of BECs with WT MV allows efficient virus production, induction of TRAIL, and subsequent widespread apoptosis.