In-cell infection: a novel pathway for Epstein-Barr virus infection mediated by cell-in-cell structures.
In-cell infection: a novel pathway for Epstein-Barr virus infection mediated by cell-in-cell structures.
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细胞内感染：细胞内结构介导的EB病毒感染的新途径
作者：
eb病毒可感染易感B淋巴细胞和非易感上皮细胞（ECs）。病毒趋向性分析揭示了EBV感染的两种有趣的方式，要么是受体介导的B细胞感染，要么是细胞间接触介导的非易感ec感染。在此，我们报告了一种新的“细胞内感染”机制，通过形成细胞内结构感染EBV非易感ec。ebv感染的Akata B细胞在体外侵袭上皮CNE-2细胞形成细胞中细胞结构。这种独特的细胞结构可以很容易地在鼻咽癌标本中观察到。重要的是，细胞中细胞结构的形成导致了Akata细胞内EBV的自主激活，随后病毒传播到CNE-2细胞，这可以通过CNE-2细胞中病毒基因的表达和病毒粒子的存在来证明。值得注意的是，细胞内感染的ECs产生的EBV表现出改变的趋向性，对B细胞和ECs都具有更高的感染功效。除了CNE-2肿瘤细胞外，细胞中细胞结构的形成也可以介导NPEC1-Bmi1细胞（一种永生化的鼻咽上皮细胞系）的EBV感染。此外，这种机制的有效感染涉及PI3K/AKT信号通路的激活。因此，我们的研究确定了“细胞内感染”作为EBV感染的新机制。考虑到病毒感染细胞的多样性和慢性感染期间细胞内结构的普遍性，我们推测“细胞内感染”可能是EBV和其他病毒感染非易感ec的一般机制。
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.
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影响因子：
9
作者：
He, M-f;Wang, S.;Wang, Y.;Wang, X-n
通讯作者：
Wang, X-n
DOI：
10.1126/science.1252786
发表时间：
2014-03-21
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Lieberman PM
通讯作者：
Lieberman PM
影响因子：
5.4
作者：
Darr, CD;Mauser, A;Kenney, S
通讯作者：
Kenney, S
影响因子：
3.6
作者：
Chen, Hong-lei;Peng, Jun;Xia, He-shun
通讯作者：
Xia, He-shun
影响因子：
5.4
作者：
BILLAUD, M;BUSSON, P;LENOIR, GM
通讯作者：
LENOIR, GM