首页> 外文期刊>Infection, Genetics and Evolution: Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases >Genetic variability in the major capsid L1 protein of human papillomavirus type 16 (HPV-16) and 18 (HPV-18)
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Genetic variability in the major capsid L1 protein of human papillomavirus type 16 (HPV-16) and 18 (HPV-18)

机译:人类乳头瘤病毒16型(HPV-16)和18型(HPV-18)的主要衣壳L1蛋白的遗传变异性

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HPV-16 and HPV-18 infections result in nearly 73% of cervical cancers worldwide. The L1 protein comprising HPV vaccine formulations elicit high-titre neutralizing antibodies. The aim of this study was to detect L1 HPV-16 and HPV-18 gene polymorphisms and analyze intratypic variations. HPV-16 (n = 29) and HPV-18 (n 5) L1 gene sequences were obtained from cervical samples harvested from Italian women. Phylogenetic trees were constructed using the Neighbor-Joining and the Kimura 2-parameters methods (MEGA software). To estimate selection pressures acting on the L1 gene, codon-specific non-synonymous (d(N)) and synonymous (d(s)) substitutions were inferred using the Nei-Gojobori method and Jukes-Cantor model (MEGA software) and integrated analyses carried out using SLAC, FEL and REL methodologies. All the HPV-16 L1 sequences analyzed fell into the European branch (99.4-99.7% similarity). Thirty-four single nucleotide changes were observed and 18 (52.9%) were non-synonymous mutations (7/18 were identified in sequences encoding an immunodominant loop and one occurred in the sequence encoding the alpha-4 domain associated with VLP conformation). There was no evidence of positive selection in the sequence alignment of L1 HPV-16 genes (P-value < 0.1). One mutation was identified in a negatively selected codon. HPV-18 L1 analyzed sequences fell into two phylogenetic branches: the HPV-18 European branch (99.5-100% similarity) and the HPV-18 African branch (99.8% similarity). Nine single nucleotide changes were observed and 4/9 (44.5%) of these nucleotide mutations were non-synonymous and one was present in a sequence encoding the immunodominant FG loop. There was no evidence of positive selection in the sequence alignment of L1 HPV-18 genes (P-value < 0.1). This study identified polymorphisms of undefined biological activity in HPV-16 and HPV-18 L1 sequences. Information regarding the genetic diversity of HPV-16 and HPV-18 L1 gene sequences may help define the oncogenic potential of respective strains and to better understand immune escape mechanisms. (C) 2011 Elsevier B.V. All rights reserved.
机译:HPV-16和HPV-18感染导致全世界将近73%的宫颈癌。包含HPV疫苗制剂的L1蛋白引发高滴度中和抗体。这项研究的目的是检测L1 HPV-16和HPV-18基因多态性并分析基因型变异。 HPV-16(n = 29)和HPV-18(n 5)L1基因序列是从意大利女性的宫颈样本中获得的。使用Neighbor-Joining和Kimura 2参数方法(MEGA软件)构建系统发育树。为了估计作用于L1基因的选择压力,使用Nei-Gojobori方法和Jukes-Cantor模型(MEGA软件)推断了密码子特异性的非同义(d(N))和同义(d(s))取代,并进行了整合使用SLAC,FEL和REL方法进行的分析。分析的所有HPV-16 L1序列均落入欧洲分支(99.4-99.7%相似)。观察到34个单核苷酸变化,其中18个(52.9%)是非同义突变(在编码免疫优势环的序列中鉴定出7/18,在编码与VLP构象相关的α-4结构域的序列中鉴定出一个)。 L1 HPV-16基因的序列比对中没有阳性选择的证据(P值<0.1)。在阴性选择的密码子中鉴定出一种突变。 HPV-18 L1分析的序列分为两个系统发育分支:HPV-18欧洲分支(99.5-100%相似性)和HPV-18非洲分支(99.8%相似性)。观察到九个单核苷酸变化,并且这些核苷酸突变的4/9(44.5%)是非同义词的,并且在编码免疫显性FG环的序列中存在一个。 L1 HPV-18基因的序列比对中没有阳性选择的证据(P值<0.1)。这项研究确定了HPV-16和HPV-18 L1序列中生物学活性不确定的多态性。有关HPV-16和HPV-18 L1基因序列遗传多样性的信息可能有助于确定各个菌株的致癌潜力,并更好地了解免疫逃逸机制。 (C)2011 Elsevier B.V.保留所有权利。

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