Sequence analysis of the long control region of human papillomavirus type 16 variants and functional consequences for P97 promoter activity
Sequence analysis of the long control region of human papillomavirus type 16 variants and functional consequences for P97 promoter activity
复制标题
DOI：
10.1099/0022-1317-81-8-1975
复制
发表时间：
2000-08-01
影响因子：
3.8
通讯作者：
Pfister, H
中科院分区：
文献类型：
--
作者：
Kämmer, C;Warthorst, U;Pfister, H
生殖器人类乳头瘤病毒（HPV）被认为是宫颈癌发展的主要危险因素之一。P97启动子位于长控制区（LCR）的E6-近端，调控病毒基因的转录，尤其是致癌基因E6和E7。LCR含有几种病毒和细胞转录因子的结合位点，这些转录因子激活或抑制P97启动子。HPV-16型内变异属于分布在世界各地的6个地理聚集的系统发育群。这些变异在体内表现出E6蛋白活性和肿瘤进展的差异。通过测序整个LCR （nt 7060-124）并比较其P97启动子的转录活性，研究了7个HPV-16变异体。在所有被调查的lcr中发现了以前未知的核苷酸变异。在荧光素酶测定中，与欧洲参考克隆相比，在亚洲美洲c和北美1变异中检测到的P97启动子活性增加了3.3倍和2.8倍。非洲变异1a和2a表现出与欧洲参考克隆相当的P97启动子活性。重组不同的LCR片段后，在亚洲美洲c和北美1变异中负责转录增强的区域可归因于LCR的e6近端（nt 7619-124）。
Genital human papillomaviruses (HPV) are considered to be one of the main risk factors for the development of cervical cancer. The P97 promoter at the E6-proximal end of the long control region (LCR) regulates the transcription of viral genes, especially the oncogenes E6 and E7. The LCR contains binding sites of several viral and cellular transcription factors, which either activate or repress the P97 promoter. Intratype variants of HPV-16 belong to six geographically clustered phylogenetic groups distributed all over the world. These variants exhibit differences in E6 protein activities and in tumour progression in vivo. Seven HPV-16 variants were investigated by sequencing the entire LCR (nt 7060-124) and by comparing the transcriptional activities of their P97 promoters. Previously unknown nucleotide variations were identified in all LCRs investigated. In luciferase assays, 3.3- and 2.8-fold increases in P97 promoter activity were detected in the Asian American c and North American 1 variants when compared with the European reference clone. The African variants 1a and 2a exhibited P97 promoter activities comparable to the European reference clone. After recombining different LCR fragments, the region responsible for enhanced transcription in the Asian American c and North American 1 variants could be attributed to the E6-proximal end of the LCR (nt 7619-124).