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题目:
In-cell infection: a novel pathway for Epstein-Barr virus infection mediated by cell-in-cell structures.
作者:
Ni(Chao),Chen(Yuhui),Zeng(Musheng),Pei(Rongjuan),Du(Yong),Tang(Linquan),Wang(Mengyi),Hu(Yazhuo),Zhu(Hanyu),He(Meifang),Wei(Xiawei),Wang(Shan),Ning(Xiangkai),Wang(Manna),Wang(Jufang),Ma(Li),Chen(Xinwen),Sun(Qiang),Tang(Hong),Wang(Ying),Wang(Xiaoning)
状态:
发布时间2015-07-03 , 更新时间 2015-07-08
期刊:
Cell Res
摘要:
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.
语言:
eng
DOI:

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