Characterization of human papillomavirus type 57b: Transforming activity and comparative sequence analysis as probes for biological determinants associated with high-risk oncogenic viruses
Characterization of human papillomavirus type 57b: Transforming activity and comparative sequence analysis as probes for biological determinants associated with high-risk oncogenic viruses
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DOI：
10.1007/bf00572955
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发表时间：
1996-01-01
期刊：
影响因子：
1.6
通讯作者：
Mounts, P
中科院分区：
文献类型：
--
作者：
Trujillo, JM;Wu, TC;Mounts, P
先前报道了人乳头瘤病毒57型（HPV-57）与鼻腔的癌前和恶性肿瘤的关联（Wu等人，Lancet 341，522，1993）。我们确定了HPV-57 b（GenBank 37537）的完整核苷酸序列，其是从良性真菌状乳头状瘤分子克隆的，并将其与其他HPV类型和HPV-57 a进行了比较，HPV-57 a是de Villiers等人从上颌窦内翻性乳头状瘤克隆的（Virology 171，248. 1989年）。将HPV-57 b癌基因E5、E6和E7的氨基酸序列与HPV-6、11、16和18进行比较和系统发育分析。使用Jotun-Hein算法的系统发生树表明HPV-57 b E5和E7与HPV-18的相应基因的关系更近。这两种癌基因的特征模式分析也与HPV-16和18癌基因的密切相关性一致，这些癌基因与恶性进展的高风险相关。与HPV-57 a的7861 bp相比，HPV-57 b的长度为7868 bp，限制性酶切位点和开放阅读框存在差异，至少增加了5个。为了研究HPV-57 b的致癌潜力，NIH 3 T3和REF 52细胞用两种质粒共转染：pKP54.HPV-57 b，其含有HPV-57 b基因组，和pMT.neo.1，其赋予对G418的抗性。在含有G418的培养基中选择后，58%的G418（r）NIH 3 T3集落和47%的G418（r）REF 52集落表现出形态转化。这些结果表明，转录调控元件和癌蛋白的HPV-57 b是活跃的体外诱导细胞转化，是其他高危型HPV。
The association of human papillomavirus type 57 (HPV-57) with premalignant and malignant tumors of the nasal cavity was previously reported (Wu et al., Lancet 341, 522, 1993). We determined the complete nucleotide sequence of HPV-57b (GenBank 37537), which was molecularly cloned from a benign fungiform papilloma, and compared it with other HPV types and HPV-57a, which was cloned from an inverted papilloma of the maxillary sinus by de Villiers et al. (Virology 171, 248. 1989). Comparative and phylogenetic analysis of amino acid sequences of the HPV-57b oncogenes E5, E6, and E7 were performed with HPV-6, 11, 16, and 18. Phylogenetic trees using the Jotun-Hein algorithm indicated a closer relationship of HPV-57b E5 and E7 with corresponding genes of HPV-18. Signature pattern analysis of these two oncogenes was also in agreement with a closer relatedness to HPV-16 and 18 oncogenes, which are associated with a high risk for malignant progression. Compared with 7861 bp of HPV-57a, HPV-57b had 7868 bp as well as differences in the restriction enzyme sites and the open reading frames, including at least five additional ones. To investigate the oncogenic potential of HPV-57b, NIH 3T3 and REF52 cells were cotransfected with two plasmids: pKP54.HPV-57b, which contains the HPV-57b genome, and pMT.neo.1, which confers resistance to G418. After selection in culture medium containing G418, 58% of the G418(r) NIH 3T3 colonies and 47% of the G418(r) REF52 colonies exhibited morphological transformation. These results indicate that the transcriptional regulatory elements and the oncoproteins of HPV-57b are active in vitro to induce cellular transformation, as are other high-risk HPV types.