Pillai M R, Hariharan R, Babu Janki Mohan, Lakshmi S, Chiplunkar S V, Patkar M, Tongaonkar H, Dinshaw K, Jayshree R S, Reddy B K M, Siddiqui M, Roychoudury Soma, Saha Baisakhi, Abraham P, Gnanamony M, Peedicayil A, Subhashini J, Ram T S, Dey Bindu, Sharma C, Jain S K, Singh N
Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, India.
Int J Cancer. 2009 Jul 1;125(1):91-103. doi: 10.1002/ijc.24322.
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 H78Y (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 of HPV diagnostics, vaccine, and for therapeutic purpose.
人乳头瘤病毒是宫颈癌病因中的一个致病因素，其中HPV16是与之相关的最常见基因型。HPV 16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，还与病毒持续存在和进展的风险相关。这项多中心研究的目的是确定在印度流行的HPV-16 E6、E7和L1变体及其可能的生物学效应。从印度的6个中心收集了宫颈鳞状细胞癌活检样本，并检测了HPV 16的存在情况。通过对412个样本中L1、E6和E7基因的全长序列分析，对HPV-16变体进行了特征描述。不同中心/地区的变体分布相似，欧洲变体E350G最为常见（58%），其次是美亚变体（11.4%）。在E6区域发现了56处变化，其中31处为非同义变化。最常见的是L83V（72.3%）、Q14H（13.1%）和H78Y（12.1%）。在E7区域发现了29处改变，其中12处为非同义改变。最常见的是F57V（9%）。L1区域显示有204处变化，其中67处为非同义变化。最常见的是448insS（100%）、465delD（100%）、H228D（94%）、T292A（85%）。所确定的变体有些是新的，有些是已报道的，它们可能会破坏五聚体形成、病毒的转录调控、L1蛋白界面相互作用、B细胞和T细胞表位、p53降解，因此它们的分布对于HPV诊断、疫苗的开发以及治疗目的都很重要。
