EPSTEIN-BARR-VIRUS INFECTION AND REPLICATION IN A HUMAN EPITHELIAL-CELL SYSTEM

EPSTEIN-BARR-VIRUS INFECTION AND REPLICATION IN A HUMAN EPITHELIAL-CELL SYSTEM
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DOI:
10.1038/356347a0
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发表时间:
1992-03-26
期刊:
影响因子:
64.8
通讯作者:
RICKINSON, AB
RICKINSON, AB
中科院分区:
综合性期刊1区
文献类型:
--
作者:
LI, QX;YOUNG, LS;RICKINSON, AB

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EPSTEIN-BARR病毒是一种具有致癌潜力的人疱疹病毒,在体内感染两种靶组织:B淋巴细胞,其中感染主要是非生产性的1,以及病毒复制发生的复层鳞状上皮2,3。通过病毒与B细胞表面分子CR2的结合而引发的与B细胞的相互作用(参考文献4)已在体外进行了研究,并定义了与B细胞生长转化相关的病毒“潜伏”基因5。相比之下,上皮细胞的病毒感染仍然知之甚少,反映了缺乏适当的细胞培养模型。在这里,我们描述了这样一个模型的发展,使用作为目标的CR2表达转染细胞的两个独立的人上皮细胞系。这些细胞中的高比例结合病毒并变得活跃感染,表达小EBER RNA(小的非多聚腺苷酸化病毒编码RNA)和Epstein-Barr核抗原1,但不表达其他潜伏蛋白;此后,在有利于上皮分化的条件下,可以诱导高达30%的细胞进入病毒生产周期,其中一些进展到完全病毒复制。我们发现实验室病毒株感染上皮细胞的能力与其B细胞生长转化活性之间存在显着差异。
EPSTEIN-BARR virus, a human herpesvirus with oncogenic potential, infects two target tissues in vivo: B lymphocytes, where the infection is largely non-productive 1, and stratified squamous epithelium in which virus replication occurs 2,3. The interaction with B cells, initiated through virus binding to the B-cell surface molecule CR2 (ref. 4), has been studied in vitro and the virus 'latent' genes associated with B-cell growth transformation defined 5. By comparison, viral infection of epithelium remains poorly understood, reflecting the lack of an appropriate cell-culture model. Here we describe the development of such a model using as targets CR2-expressing transfected cells of two independent human epithelial lines. A high proportion of these cells bind virus and become actively infected, expressing the small EBER RNAs (small non-polyadenylated virus-coded RNAs) and the Epstein-Barr nuclear antigen 1 but not other latent proteins; thereafter, under conditions favouring epithelial differentiation, up to 30% of the cells can be induced to enter virus productive cycle with some progressing to full virus replication. We find significant differences between laboratory virus strains in their ability to infect epithelium that do not correlate with their B-cell growth-transforming activity.