Cell-to-cell contact as an efficient mode of Epstein-Barr virus infection of diverse human epithelial cells
Cell-to-cell contact as an efficient mode of Epstein-Barr virus infection of diverse human epithelial cells
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DOI：
10.1128/jvi.72.5.4371-4378.1998
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发表时间：
1998-05-01
影响因子：
5.4
通讯作者：
Takada, K
中科院分区：
文献类型：
--
作者：
Imai, S;Nishikawa, J;Takada, K
我们显示了明确的证据，各种人类上皮细胞的体外EB病毒（EBV）的直接感染。通过使用携带选择性标记基因的重组EBV（Akata株）而不进行任何其它人工操作（例如引入已知的EBV受体（CD 21）基因或在培养物中添加针对病毒gp 350的多聚免疫球蛋白A）来实现成功感染。在检测的21个人上皮细胞系中，18个被EBV感染，如通过在病毒暴露后的早期检测EBV确定的核抗原（EBNA）1表达所确定的，并且随后的选择培养容易地从15个细胞系中产生许多EBV感染的克隆。没有人成纤维细胞和五个非人源性细胞系检查是易感的感染。相比之下，与病毒生产者共培养显示出比无细胞感染高出约800倍的感染效率，这表明细胞与细胞直接接触作为体内病毒传播模式的重要性。大多数感染EBV的上皮细胞系在蛋白质和mRNA水平上CD 21表达阴性。从每个细胞系建立的大多数EBV感染的克隆总是表达EBNA 1、EBV编码的小RNA、来自病毒基因组的BamHI-A区域的转录本和潜伏膜蛋白（LMP）2A，但不表达其他EBNA或LMP 1。这种限制性形式的潜伏病毒基因表达，这是一个核心问题，了解上皮癌的EBV，类似于在EBV相关的胃癌和LMP 1阴性鼻咽癌。结果表明，EB病毒直接感染上皮细胞可能在体内自然发生，这可能是由一个未鉴定的，上皮特异性结合受体的EB病毒介导的，EBV转化体被视为，至少在病毒基因表达方面，在体外类似物的EB病毒相关的上皮肿瘤细胞，从而促进分析的致癌作用的EB病毒在上皮细胞。
We show clear evidence for direct infection of various human epithelial cells by Epstein-Barr virus (EBV) in vitro. The successful infection was achieved by using recombinant EBV (Akata strain) carrying a selective marker gene but without any other artificial operations, such as introduction of the known EBV receptor (CD21) gene or addition of polymeric immunoglobulin A against viral gp350 in culture. Of 21 human epithelial cell lines examined, 18 became infected by EBV, as ascertained by the detection of EBV-determined nuclear antigen (EBNA) 1 expression in the early period after virus exposure, and the following selection culture easily yielded a number of EBV-infected clones from 15 cell lines. None of the human fibroblasts and five nonhuman-derived cell lines examined was susceptible to the infection. By comparison, cocultivation with virus producers showed approximate to 800-fold-higher efficiency of infection than cell-free infection did, suggesting the significance of direct cell-to-cell contact as a mode of virus spread in vivo. Most of the epithelial cell lines infectable with EBV were negative for CD21 expression at the protein and mRNA levels. The majority of EBV-infected clones established from each cell line invariably expressed EBNA1, EBV-encoded small RNAs, rightward transcripts from the BamHI-A region of the virus genome, and latent membrane protein (LMP) 2A, but not the other EBNAs or LMP1. This restricted form of latent viral gene expression, which is a central issue for understanding epithelial oncogenesis by EBV, resembled that seen in EBV-associated gastric carcinoma and LMP1-negative nasopharyngeal carcinoma. The results indicate that direct infection of epithelial cells by EBV may occur naturally in vivo, and this could be mediated by an unidentified, epithelium-specific binding receptor for EBV, The EBV convertants are viewed, at least in terms of viral gene expression, as in vitro analogs of EBV-associated epithelial tumor cells, thus facilitating analysis of an oncogenic role(s) for EBV in epithelial cells.