机构:[1]Institute of Life Sciences, Chinese PLA General Hospital and School of Bioscience and Bioengineering, South China University of Technology, Key Laboratory of Normal aging and Geriatric & the State Key Laboratory of Kidney, Beijing 100853 &the Provincial Key Laboratory of Biotechnology, Guangdong 510006, China.[2]State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, China.[3]Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071, China.[4]School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.[5]State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.四川大学华西医院[6]The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510260, China.[7]Laboratory of Cell Engineering, Institute of Biotechnology, Beijing 100071, China.[8]Institute of Molecular Immunology, School of Biotechnology, Southern Medical University, Guangzhou, Guangdong 510515, China.[9]Department of Immunology and Microbiology, Shanghai Institute of Immunology, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
Epstein-Barr virus (EBV) can infect both susceptible B lymphocytes and non-susceptible epithelial cells (ECs). Viral tropism analyses have revealed two intriguing means of EBV infection, either by a receptor-mediated infection of B cells or by a cell-to-cell contact-mediated infection of non-susceptible ECs. Herein, we report a novel "in-cell infection" mechanism for EBV infection of non-susceptible ECs through the formation of cell-in-cell structures. Epithelial CNE-2 cells were invaded by EBV-infected Akata B cells to form cell-in-cell structures in vitro. Such unique cellular structures could be readily observed in the specimens of nasopharyngeal carcinoma. Importantly, the formation of cell-in-cell structures led to the autonomous activation of EBV within Akata cells and subsequent viral transmission to CNE-2 cells, as evidenced by the expression of viral genes and the presence of virion particles in CNE-2 cells. Significantly, EBV generated from in-cell infected ECs displayed altered tropism with higher infection efficacy to both B cells and ECs. In addition to CNE-2 tumor cells, cell-in-cell structure formation could also mediate EBV infection of NPEC1-Bmi1 cells, an immortalized nasopharyngeal epithelial cell line. Furthermore, efficient infection by this mechanism involved the activation of the PI3K/AKT signaling pathway. Thus, our study identified "in-cell infection" as a novel mechanism for EBV infection. Given the diversity of virus-infected cells and the prevalence of cell-in-cell structures during chronic infection, we speculate that "in-cell infection" is likely a general mechanism for EBV and other viruses to infect non-susceptible ECs.
基金:
This work was funded
by the National Natural Science Foundation of China (81273197
and 81471578 to XNW and 81472588 to QS) and the Ministry of
Science and Technology of China (973 Program; 2013CB530506
to YW and 2015CB050449 to QS).
第一作者机构:[1]Institute of Life Sciences, Chinese PLA General Hospital and School of Bioscience and Bioengineering, South China University of Technology, Key Laboratory of Normal aging and Geriatric & the State Key Laboratory of Kidney, Beijing 100853 &the Provincial Key Laboratory of Biotechnology, Guangdong 510006, China.
共同第一作者:
通讯作者:
推荐引用方式(GB/T 7714):
Ni Chao,Chen Yuhui,Zeng Musheng,et al.In-cell infection: a novel pathway for Epstein-Barr virus infection mediated by cell-in-cell structures.[J].CELL RESEARCH.2015,25(7):785-800.doi:10.1038/cr.2015.50.
APA:
Ni Chao,Chen Yuhui,Zeng Musheng,Pei Rongjuan,Du Yong...&Wang Xiaoning.(2015).In-cell infection: a novel pathway for Epstein-Barr virus infection mediated by cell-in-cell structures..CELL RESEARCH,25,(7)
MLA:
Ni Chao,et al."In-cell infection: a novel pathway for Epstein-Barr virus infection mediated by cell-in-cell structures.".CELL RESEARCH 25..7(2015):785-800