Differentiation-induced changes in promoter usage for transcripts encoding the human papillomavirus type 31 replication protein E1
Differentiation-induced changes in promoter usage for transcripts encoding the human papillomavirus type 31 replication protein E1
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DOI：
10.1006/viro.1999.9636
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发表时间：
1999-04-25
期刊：
影响因子：
3.7
通讯作者：
Laimins, LA
中科院分区：
文献类型：
--
作者：
Klumpp, DJ;Laimins, LA
人乳头瘤病毒 (HPV) 的生命周期与角质形成细胞的分化有关。病毒生命周期中的一项关键事件是病毒复制的分化依赖性增加。复制活性的增加导致 HPV 基因组从基底角质形成细胞中每个细胞约 50 个拷贝扩增到基底上角质形成细胞中每个细胞数千个病毒基因组拷贝。为了表征与这种分化依赖性 HPV 复制增加相关的事件，我们开始研究在稳定维持附加型 HPV DNA 的细胞系分化过程中编码 HPV 复制蛋白 E1 的 mRNA。分化诱导了与 E1 特异性探针杂交的几种转录物的表达。其中一条信息（3.7 kb 转录本）不与 E6 开放阅读框上游早期启动子特异性探针杂交。 RNase 保护分析证实了来自 E7 开放阅读框中间第 742 号核苷酸处的分化依赖性启动子的未剪接信息的诱导。这些观察结果表明，分化诱导的来自病毒晚期启动子的 E1 mRNA 增加，并表明 E1 表达增加在 HPV 基因组扩增过程中发挥了作用。 (C) 1999 年学术出版社。
The life cycle of human papillomaviruses (HPVs) is tied to keratinocyte differentiation. One key event in the viral life cycle is the differentiation-dependent increase in viral replication. This increase in replication activity results in an amplification of the HPV genome from approximately 50 copies per cell in basal keratinocytes to thousands of copies of the Viral genome per cell in suprabasal keratinocytes. To characterize the events associated with this differentiation-dependent increase in HPV replication, we have initiated studies of mRNAs encoding the HPV replication protein E1 during the differentiation of cell lines that stably maintain episomal HPV DNA. Differentiation induced the expression of several transcripts that hybridized to an E1-specific probe. One of these messages, a 3.7-kb transcript, did not hybridize to a probe specific for the early promoter upstream of the E6 open reading frame. RNase protection analysis confirmed an induction of unspliced messages derived from the differentiation-dependent promoter at nucleotide 742 in the middle of the E7 open reading frame. These observations demonstrate a differentiation-induced increase in E1 mRNAs derived from the viral late promoter and suggest a role for increased E1 expression during amplification of the HPV genome. (C) 1999 Academic Press.