Genetic variability in L1 and L2 genes of HPV-16 and HPV-58 in Southwest China.
Genetic variability in L1 and L2 genes of HPV-16 and HPV-58 in Southwest China.
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中国西南地区HPV-16和HPV-58 L1和L2基因的遗传变异
DOI：
10.1371/journal.pone.0055204
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Li Q
中科院分区：
文献类型：
--
作者：
Yue Y;Yang H;Wu K;Yang L;Chen J;Huang X;Pan Y;Ruan Y;Zhao Y;Shi X;Sun Q;Li Q
HPV占宫颈癌发病率的大部分。大约90%的肛门癌和较小的子集（<50%）的其他癌症（口咽，阴茎，阴道，外阴）也归因于HPV。包含L1蛋白的HPV疫苗制剂产生高滴度中和抗体并赋予类型限制性保护。L2蛋白是广泛保护性HPV疫苗的有希望的候选者。我们在前期的研究中发现，西南地区女性高危型HPV感染以HPV-16和HPV-58最多见。为探讨中国西南地区HPV-16和HPV-58 L1/L2基因的多态性和基因内变异，对中国西南地区HPV-16（L1：n = 31，L2：n = 28）和HPV-58（L1：n = 21，L2：n = 21）L1/L2基因进行测序，并与GenBank中已发表的文献进行比较。 然后用邻接法和Kimura 2-parameters法（MEGA软件）构建系统发育树，并分析二级结构的多样性。利用PAML软件估算了L1/L2基因的选择压力。在HPV-16 L1序列中观察到29个单核苷酸变化，其中16/29个非同义突变和13/29个同义突变（6个在α螺旋中，2个在β转角中）。在HPV-16 L2序列中观察到17个单核苷酸变化，其中8/17个非同义突变（1个在β转角）和9/17个同义突变。在HPV-58 L1序列中观察到24个单核苷酸变化，其中10/24个非同义突变和14/24个同义突变（8个在α螺旋，4个在β转角）。在HPV-58 L2序列中观察到7个单核苷酸变化，其中4/7个非同义突变和3/7个同义突变。选择压力分析结果表明，这些突变多为正选择。本研究有助于了解HPV-16/HPV-58的内在地理相关性和生物学差异，并有助于进一步研究其感染性、致病性和疫苗策略。
HPV account for most of the incidence of cervical cancer. Approximately 90% of anal cancers and a smaller subset (<50%) of other cancers (oropharyngeal, penile, vaginal, vulvar) are also attributed to HPV. The L1 protein comprising HPV vaccine formulations elicits high-titre neutralizing antibodies and confers type restricted protection. The L2 protein is a promising candidate for a broadly protective HPV vaccine. In our previous study, we found the most prevalent high-risk HPV infectious serotypes were HPV-16 and HPV-58 among women of Southwest China. To explore gene polymorphisms and intratypic variations of HPV-16 and HPV-58 L1/L2 genes originating in Southwest China, HPV-16 (L1: n = 31, L2: n = 28) and HPV-58 (L1: n = 21, L2: n = 21) L1/L2 genes were sequenced and compared to others described and submitted to GenBank. Phylogenetic trees were then constructed by Neighbor-Joining and the Kimura 2-parameters methods (MEGA software), followed by an analysis of the diversity of secondary structure. Then selection pressures acting on the L1/L2 genes were estimated by PAML software. Twenty-nine single nucleotide changes were observed in HPV-16 L1 sequences with 16/29 non-synonymous mutations and 13/29 synonymous mutations (six in alpha helix and two in beta turns). Seventeen single nucleotide changes were observed in HPV-16 L2 sequences with 8/17 non-synonymous mutations (one in beta turn) and 9/17 synonymous mutations. Twenty-four single nucleotide changes were observed in HPV-58 L1 sequences with 10/24 non-synonymous mutations and 14/24 synonymous mutations (eight in alpha helix and four in beta turn). Seven single nucleotide changes were observed in HPV-58 L2 sequences with 4/7 non-synonymous mutations and 3/7 synonymous mutations. The result of selective pressure analysis showed that most of these mutations were of positive selection. This study may help understand the intrinsic geographical relatedness and biological differences of HPV-16/HPV-58 and contributes further to research on their infectivity, pathogenicity, and vaccine strategy.
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影响因子：
51.1
作者：
de Sanjose, Silvia;Quint, Wim G. V.;Xavier Bosch, F.
通讯作者：
Xavier Bosch, F.
影响因子：
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