Genetic variability of human papillomavirus type 51 E6, E7, L1 and L2 genes in Southwest China

• Published in: Gene Vol. 690; pp. 99 - 112
• Main Authors: Xu, Jianju, Tan, Liping, Wang, Tao, Cui, Fangying, Ding, Xianping, Wan, Qiuling, Deng, Dan, Chen, Zuyi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30.03.2019
• Subjects: amino acids; Cervical cancer; China; computer software; DNA; E6, E7, L1 and L2 genes; Genetic variability; genetic variation; HPV51; Internet; Lineage phylogeny; mutation; oncogenes; Papillomaviridae; phylogeny; selection pressure; Southwest China; statistical analysis; China; Genetic variability; Southwest China; HPV51; E6, E7, L1 and L2 genes; Cervical cancer; Lineage phylogeny
• ISSN: 0378-1119; 1879-0038; 1879-0038
• DOI: 10.1016/j.gene.2018.12.032

Genetic variations among HR-HPV types lead to altered biological functions with possible clinical significance in different geographical locations. To explore intratype genetic variations of HPV51 E6, E7, L1 and L2 genes originating from Southwest China, a total of 5204 cervical scraped cell samples were collected for DNA extraction and HPV typing. And then the E6, E7, L1 and L2 genes of HPV51 (n = 79) were sequenced and compared to the reference sequence (M62877). The ConSurf server was used for identification of conserved structural and functional amino acids of the E6 and E7 oncogenes, and the changes of the secondary structure were analyzed by PSIPred software. Phylogenetic trees were constructed by the maximum likelihood method implemented in IQ-TREE. The selection pressure acting on the E6, E7, L1 and L2 genes was estimated by Datamonkey web server. 13 nucleotide polymorphism sites were observed in E6-E7 gene and the most common mutation sites were C395T (S100L), C756T (S66L), C796T, A832G. 36 nucleotide polymorphism sites were identified in full length L1 gene and the non-synonymous mutations T6311G, A6312T (V264G), G6313A (G265S) A5674C (I52L), A6335C (N272T), A6586C (T354P) and synonymous mutations A5649T, C6147T, A6435G, G6570A, A6651G, T6774C, A6784C, A6882G, C6918A, and G6984A were the most common mutations. 53 nucleotide variation sites were identified in full-length L2 gene including four insertion sites (4418A, 4670G, 4693A, 4694C) and one deletion site (A4430). Besides, the non-synonymous mutations G4227A (V32I), A4407G (I92V), G4945A (D271N), C4985A (T284K), T5260G (L376V), A5335C (T401P) and the synonymous mutations A4166G, G4229A, G4283A, T4453C, C4566A, T4596C, C4695T, C4830T, G4839A, A5160C, and T5286G were the most common mutations. Specially, a triallelic mutation site (G4461C/A) in L2 was identified, with 26% G4461C (E109D) being non-synonymous mutation. Selective pressure analysis showed that only codon site 66 in E7 and 52 in L1 were the positively selected sites and codon sites 72, 107, 342, 412, 427 were negatively selected sites in L2 gene. Our investigation also suggests that A2 and A4 were the most frequent HPV51 lineage in Southwest China. •It is the first study to identify the genetic variability of HPV51 E6, E7, L1 and L2 genes in Southwest China.•The majorly prevailing isolates and the major mutations of HPV51 E6, E7, L1 and L2 in Southwest China were identified.•The major nonsynonymous mutations identified in L1 were all located in immunodominant loop structures.•Several major mutations in L2 were discovered at conserved cross-reacting epitopes regions and other vital functional regions.•Some variations identified are predicted to result in functional protein changes, which could have clinical implications.