title: Neuropilin 1 is an entry factor that promotes EBV infection of nasopharyngeal epithelial cells.
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 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.
authors: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, People's Republic of China.
authors: Hong-Bo
authors: HB
authors: Wang
authors: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, People's Republic of China.
authors: Hua
authors: H
authors: Zhang
authors: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, People's Republic of China.
authors: Jing-Ping
authors: JP
authors: Zhang
authors: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, People's Republic of China.
authors: Yan
authors: Y
authors: Li
authors: Department of Medicine and Microbiology and Molecular Genetics, Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors: Bo
authors: B
authors: Zhao
authors: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, People's Republic of China.
authors: Guo-Kai
authors: GK
authors: Feng
authors: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, People's Republic of China.
authors: Yong
authors: Y
authors: Du
authors: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, People's Republic of China.
authors: Dan
authors: D
authors: Xiong
authors: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, People's Republic of China.
authors: Qian
authors: Q
authors: Zhong
authors: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, People's Republic of China.
authors: Wan-Li
authors: WL
authors: Liu
authors: College of Biotechnology, Southwest University, Chongqing 400715, People's Republic of China.
authors: Huamao
authors: H
authors: Du
authors: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, People's Republic of China.
authors: Man-Zhi
authors: MZ
authors: Li
authors: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, People's Republic of China.
authors: Wen-Lin
authors: WL
authors: Huang
authors: Department of Anatomy and Center for Cancer Research, University of Hong Kong, Hong Kong, SAR, People's Republic of China.
authors: Sai Wah
authors: SW
authors: Tsao
authors: Department of Microbiology and Immunology, Louisiana State University, Health Science Center, Shreveport, Louisiana 71130, USA.
authors: Lindsey
authors: L
authors: Hutt-Fletcher
authors: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, People's Republic of China.
authors: Yi-Xin
authors: YX
authors: Zeng
authors: Department of Medicine and Microbiology and Molecular Genetics, Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors: Elliott
authors: E
authors: Kieff
authors: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, People's Republic of China.
authors: Mu-Sheng
authors: MS
authors: Zeng
mesh_terms: D002277:Carcinoma; D045744:Cell Line, Tumor; D004705:Endocytosis; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D020031:Epstein-Barr Virus Infections / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D066246:ErbB Receptors / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D008561:Membrane Fusion; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D039942:Neuropilin-1 / Q000378:metabolism*; D039943:Neuropilin-2 / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D015398:Signal Transduction; D053586:Virus Internalization
chemical_list: D006023:Glycoproteins; D039943:Neuropilin-2; D039942:Neuropilin-1; D066246:ErbB Receptors