Molecular variants of HPV-16 associated with cervical cancer in Indian population
Molecular variants of HPV-16 associated with cervical cancer in Indian population
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DOI：
10.1002/ijc.24322
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发表时间：
2009-07-01
影响因子：
6.4
通讯作者：
Singh, N.
中科院分区：
文献类型：
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作者：
Pillai, M. R.;Hariharan, R.;Singh, N.
人乳头瘤病毒是宫颈癌病因学中的一个致病因素，HPV16是与之相关的最普遍的基因型。HPV 16的致癌性E6/E7和衣壳L1蛋白的型内变异除了具有系统发育重要性外，还与病毒持续和进展的风险相关。这项多中心研究的目的是鉴定印度流行的HPV-16 E6、E7和L1变异及其可能的生物学效应。从印度的6个中心收集了宫颈癌的鳞状细胞活检，并检查了HPV 16的存在。对412例HPV-16的L1、E6和E7基因进行了全序列分析。从不同的中心/地区看到相似的变种分布，欧洲变种E350G是最普遍的（58%），其次是美洲亚洲变种（11.4%）。E6区域有56个变化，其中31个是非同义的。最常见的是L83V (72.3%), Q14H（13.1%）和H78V（12.1%）。E7区有29个变化，其中12个是非同义的。最常见的是F57V（9%）。L1区有204个变化，其中67个为非同义。最常见的是448insS（100%）、465delD（100%）、228d（94%）、T292A（85%）。已发现的变异，有些是新的，有些是已经报道的，可以破坏五聚体的形成，病毒的转录调节，L1蛋白界面相互作用，B和T细胞表位，p53降解，因此它们的分布对于HPV诊断，疫苗和治疗目的的发展是重要的。(c) 2009年
Human papilloma virus is a causative factor in the etiology of cervical cancer with HPV16 being the most prevalent genotype associated with it. Intratype variations in oncogenic E6/E7 and capsid L1 proteins of HPV 16 besides being of phylogenetic importance, are associated with risk of viral persistence and progression. The objective of this multicentric study was to identify HPV-16 E6, E7 and L1 variants prevalent in India and their possible biological effects. Squamous cell cervical cancer biopsies were collected from 6 centres in India and examined for the presence of HPV 16. Variants of HPV-16 were characterized by full length sequence analysis of L1, E6 and E7 genes in 412 samples. Similar distribution of the variants was seen from the different centres/regions, with the European variant E350G being the most prevalent (58%), followed by American Asian variant (11.4%). Fifty six changes were seen in E6 region, 31 being nonsynonymous. The most frequent being L83V (72.3%), Q14H (13.1%) and H78V (12.1%). Twenty-nine alterations were seen in E7 region, with 12 being nonsynonymous. The most frequent being F57V (9%). L1 region showed 204 changes, of which 67 were nonsynonymous. The most frequent being 448insS (100%), and 465delD (100%), H228D (94%), T292A (85%). The identified variants some new, and some already reported can disrupt pentamer formation, transcriptional regulation of the virus, L1 protein interface interaction, B and T cell epitopes, p53 degradation, and thus their distribution is important for development (if HPV diagnostics, vaccine, and for therapeutic purpose. (C) 2009 UICC