Neuropilin 1 is an entry factor that promotes EBV infection of nasopharyngeal epithelial cells.

Neuropilin 1 is an entry factor that promotes EBV infection of nasopharyngeal epithelial cells.
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Neuropilin 1是促进鼻咽上皮细胞EBV感染的进入因子

DOI:
10.1038/ncomms7240
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发表时间:
2015-02-11
影响因子:
16.6
通讯作者:
Zeng, Mu-Sheng
Zeng, Mu-Sheng
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Wang, Hong-Bo;Zhang, Hua;Zhang, Jing-Ping;Li, Yan;Zhao, Bo;Feng, Guo-Kai;Du, Yong;Xiong, Dan;Zhong, Qian;Liu, Wan-Li;Du, Huamao;Li, Man-Zhi;Huang, Wen-Lin;Tsao, Sai Wah;Hutt-Fletcher, Lindsey;Zeng, Yi-Xin;Kieff, Elliott;Zeng, Mu-Sheng

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EB病毒(Epstein-Barr virus,EBV)是B淋巴瘤和鼻咽癌的致病因子。无细胞EBV感染鼻咽上皮细胞的机制仍然是难以捉摸的。EB病毒糖蛋白B(gB)是B细胞和上皮细胞感染的关键融合蛋白,决定了非B细胞对EB病毒的易感性。在这里,我们表明,神经纤毛蛋白1(NRP 1)直接与EB病毒gB 23 -431相互作用。敲低NRP 1或用可溶性NRP 1预处理EBV均抑制EBV感染。通过过度表达或EGF治疗上调NRP 1可增强EBV感染。然而,NRP 1的同源物NRP 2削弱EBV感染。EBV通过NRP 1促进的内化和融合,以及通过巨胞饮和脂筏依赖的内吞作用进入鼻咽上皮细胞。NRP 1部分介导EBV激活的EGFR/RAS/ERK信号传导,并且NRP 1依赖性受体酪氨酸激酶(RTK)信号传导促进EBV感染。总之,NRP 1被鉴定为EBV进入因子,其协同激活RTK信号传导,随后促进鼻咽上皮细胞中的EBV感染。 EB病毒(EBV)参与包括鼻咽癌在内的一些癌症的发展。在这里,作者表明,病毒蛋白gB和宿主蛋白neuropilin 1之间的直接相互作用是EBV感染鼻咽上皮细胞所必需的。
Epstein–Barr virus (EBV) is implicated as an aetiological factor in B lymphomas and nasopharyngeal carcinoma. The mechanisms of cell-free EBV infection of nasopharyngeal epithelial cells remain elusive. EBV glycoprotein B (gB) is the critical fusion protein for infection of both B and epithelial cells, and determines EBV susceptibility of non-B cells. Here we show that neuropilin 1 (NRP1) directly interacts with EBV gB23–431. Either knockdown of NRP1 or pretreatment of EBV with soluble NRP1 suppresses EBV infection. Upregulation of NRP1 by overexpression or EGF treatment enhances EBV infection. However, NRP2, the homologue of NRP1, impairs EBV infection. EBV enters nasopharyngeal epithelial cells through NRP1-facilitated internalization and fusion, and through macropinocytosis and lipid raft-dependent endocytosis. NRP1 partially mediates EBV-activated EGFR/RAS/ERK signalling, and NRP1-dependent receptor tyrosine kinase (RTK) signalling promotes EBV infection. Taken together, NRP1 is identified as an EBV entry factor that cooperatively activates RTK signalling, which subsequently promotes EBV infection in nasopharyngeal epithelial cells. Epstein–Barr virus (EBV) is involved in the development of some cancers including nasopharyngeal carcinoma. Here, the authors show that a direct interaction between the viral protein gB and a host protein, neuropilin 1, is required for EBV infection of nasopharyngeal epithelial cells.
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