Japanese encephalitis virus disrupts cell-cell junctions and affects the epithelial permeability barrier functions.
Japanese encephalitis virus disrupts cell-cell junctions and affects the epithelial permeability barrier functions.
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DOI：
10.1371/journal.pone.0069465
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Medigeshi GR
中科院分区：
文献类型：
--
作者：
Agrawal T;Sharvani V;Nair D;Medigeshi GR
日本脑炎病毒 (JEV) 是一种嗜神经性黄病毒，可引起病毒性脑炎，导致约 20-30% 的严重感染者死亡。尽管乙脑病毒被认为是一种嗜神经病毒，但其在外周组织非神经元细胞中的复制可能在病毒传播和发病机制中发挥关键作用。我们研究了乙脑病毒感染对许多非神经元细胞的细胞连接的影响。我们发现，JEV 在感染后期影响极化上皮细胞的通透性屏障功能。上皮细胞和内皮细胞以及肝细胞中一些紧密连接蛋白和粘附连接蛋白的水平降低。尽管诱导了抗病毒反应，但屏障破坏并不是由受感染细胞的分泌因子介导的。紧密连接蛋白claudin-1的定位在JEV感染的细胞中受到严重干扰，并且claudin-1在细胞内部分与JEV共定位并靶向溶酶体降解。 JEV衣壳的单独表达显着影响这些细胞的通透性屏障功能。我们的研究结果表明，乙脑病毒感染调节非神经元细胞的细胞连接，并损害上皮细胞和内皮细胞的通透性屏障，这可能在病毒在外周组织中传播中发挥作用。
Japanese encephalitis virus (JEV) is a neurotropic flavivirus, which causes viral encephalitis leading to death in about 20–30% of severely-infected people. Although JEV is known to be a neurotropic virus its replication in non-neuronal cells in peripheral tissues is likely to play a key role in viral dissemination and pathogenesis. We have investigated the effect of JEV infection on cellular junctions in a number of non-neuronal cells. We show that JEV affects the permeability barrier functions in polarized epithelial cells at later stages of infection. The levels of some of the tight and adherens junction proteins were reduced in epithelial and endothelial cells and also in hepatocytes. Despite the induction of antiviral response, barrier disruption was not mediated by secreted factors from the infected cells. Localization of tight junction protein claudin-1 was severely perturbed in JEV-infected cells and claudin-1 partially colocalized with JEV in intracellular compartments and targeted for lysosomal degradation. Expression of JEV-capsid alone significantly affected the permeability barrier functions in these cells. Our results suggest that JEV infection modulates cellular junctions in non-neuronal cells and compromises the permeability barrier of epithelial and endothelial cells which may play a role in viral dissemination in peripheral tissues.
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影响因子：
7.8
作者：
Furuse, Mikio;Hata, Masaki;Furuse, Kyoko;Yoshida, Yoko;Haratake, Akinori;Sugitani, Yoshinobu;Noda, Tetsuo;Kubo, Akiharu;Tsukita, Shoichiro
通讯作者：
Tsukita, Shoichiro
DOI：
10.4049/jimmunol.0903587
发表时间：
2010-10-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kajino-Sakamoto R;Omori E;Nighot PK;Blikslager AT;Matsumoto K;Ninomiya-Tsuji J
通讯作者：
Ninomiya-Tsuji J
影响因子：
2.4
作者：
Kimura, T.;Sasaki, M.;Sawa, H.
通讯作者：
Sawa, H.
影响因子：
8.8
作者：
Borah, Jani;Dutta, Prafulla;Mahanta, Jagadish
通讯作者：
Mahanta, Jagadish
影响因子：
5.8
作者：
Chang, TH;Liao, CL;Lin, YL
通讯作者：
Lin, YL