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

Author

Listed:
  • Hong-Bo Wang

    (State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center)

  • Hua Zhang

    (State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center)

  • Jing-Ping Zhang

    (State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center)

  • Yan Li

    (State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center)

  • Bo Zhao

    (Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School)

  • Guo-Kai Feng

    (State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center)

  • Yong Du

    (State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center)

  • Dan Xiong

    (State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center)

  • Qian Zhong

    (State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center)

  • Wan-Li Liu

    (State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center)

  • Huamao Du

    (College of Biotechnology, Southwest University)

  • Man-Zhi Li

    (State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center)

  • Wen-Lin Huang

    (State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center)

  • Sai Wah Tsao

    (University of Hong Kong)

  • Lindsey Hutt-Fletcher

    (Louisiana State University, Health Science Center)

  • Yi-Xin Zeng

    (State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center)

  • Elliott Kieff

    (Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School)

  • Mu-Sheng Zeng

    (State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center)

Abstract

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.

Suggested Citation

  • Hong-Bo Wang & Hua Zhang & Jing-Ping Zhang & Yan Li & Bo Zhao & Guo-Kai Feng & Yong Du & Dan Xiong & Qian Zhong & Wan-Li Liu & Huamao Du & Man-Zhi Li & Wen-Lin Huang & Sai Wah Tsao & Lindsey Hutt-Flet, 2015. "Neuropilin 1 is an entry factor that promotes EBV infection of nasopharyngeal epithelial cells," Nature Communications, Nature, vol. 6(1), pages 1-13, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7240
    DOI: 10.1038/ncomms7240
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