Genetic analysis of the human papillomavirus type 31 differentiation-dependent late promoter
Genetic analysis of the human papillomavirus type 31 differentiation-dependent late promoter
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DOI：
10.1128/jvi.79.6.3309-3321.2005
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发表时间：
2005-03-01
影响因子：
5.4
通讯作者：
Meyers, C
中科院分区：
文献类型：
--
作者：
Bodily, JM;Meyers, C
人乳头瘤病毒感染分层鳞状上皮，引起良性和恶性病变。在宿主角化细胞分化后，病毒经历了DNA复制和晚期启动子转录的急剧增加，导致晚期基因的表达和病毒粒子的形态发生。在人乳头瘤病毒31型（HPV31）中，晚期启动子被指定为p742，包含嵌入在E7基因中的多个起始位点。在本报告中，我们绘制了控制p742转录活性的病毒DNA元件。病毒上游调控区的增强子元件正调控该启动子。包含转录起始位点的区域对于活性是必不可少的，并且在E6/E7区域中至少有两个独立的元件能够支持转录。其中，我们将一个映射到E7开放阅读框的150-bp区域，并将其指定为核心p742启动子。使用蛋白激酶C信号的抑制剂GF109203X，我们发现p742的激活不依赖于病毒基因组扩增。最后，我们绘制了p742区域中赋予分化响应性的元件，并表明上游调控区域对p742的分化响应没有贡献。这些研究是了解多启动子功能和调控的重要一步。
Human papillomaviruses infect stratifying squamous epithelia, causing benign and malignant lesions. Upon differentiation of the host keratinocyte, the virus undergoes a dramatic increase in both DNA replication and transcription from the late promoter, leading to expression of late genes and virion morphogenesis. In human papillomavirus type 31 (HPV31), the late promoter is designated p742 and includes multiple start sites embedded within the E7 gene. In this report, we mapped viral DNA elements that control transcriptional activity from p742. Enhancer elements in the viral upstream regulatory region positively regulate this promoter. The region containing the transcriptional start sites is dispensable for activity, and at least two separate elements in the E6/E7 region are capable of supporting transcription. Of these, we mapped one to a 150-bp region of the E7 open reading frame and designate it the core p742 promoter. Using GF109203X, an inhibitor of protein kinase C signaling, we show that p742 activation is independent of viral genome amplification. Finally, we mapped elements in the region of p742 that confer responsiveness to differentiation and show that the upstream regulatory region does not contribute to the differentiation response of p742. These studies are an important step toward understanding the functioning and regulation of this multiple-start promoter.