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Neuropilin 1 is an entry factor that promotes EBV infection of nasopharyngeal epithelial cells
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 cel...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Pub. Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4339892/ https://www.ncbi.nlm.nih.gov/pubmed/25670642 http://dx.doi.org/10.1038/ncomms7240 |
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author | 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 |
author_facet | 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 |
author_sort | Wang, Hong-Bo |
collection | PubMed |
description | 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 gB(23–431). 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. |
format | Online Article Text |
id | pubmed-4339892 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Pub. Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-43398922015-03-02 Neuropilin 1 is an entry factor that promotes EBV infection of nasopharyngeal epithelial cells 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 Nat Commun Article 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 gB(23–431). 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. Nature Pub. Group 2015-02-11 /pmc/articles/PMC4339892/ /pubmed/25670642 http://dx.doi.org/10.1038/ncomms7240 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article 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 Neuropilin 1 is an entry factor that promotes EBV infection of nasopharyngeal epithelial cells |
title | Neuropilin 1 is an entry factor that promotes EBV infection of nasopharyngeal epithelial cells |
title_full | Neuropilin 1 is an entry factor that promotes EBV infection of nasopharyngeal epithelial cells |
title_fullStr | Neuropilin 1 is an entry factor that promotes EBV infection of nasopharyngeal epithelial cells |
title_full_unstemmed | Neuropilin 1 is an entry factor that promotes EBV infection of nasopharyngeal epithelial cells |
title_short | Neuropilin 1 is an entry factor that promotes EBV infection of nasopharyngeal epithelial cells |
title_sort | neuropilin 1 is an entry factor that promotes ebv infection of nasopharyngeal epithelial cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4339892/ https://www.ncbi.nlm.nih.gov/pubmed/25670642 http://dx.doi.org/10.1038/ncomms7240 |
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