Genetic variability of human papillomavirus type 39 based on E6, E7 and L1 genes in Southwest China

Abstract

Background Human papillomavirus type 39 associated with genital intraepithelial neoplasia and invasive cancers, has a high prevalence in Southwest China. HPV E6, E7 are two main papillomavirus oncoproteins, closely relate to the function of HPV immortalization, cell transformation, and carcinogenesis. L1 is the major capsid protein, can reflect the replication status of the virus in cells and the progression of cervical lesions. The purpose of this study is to reveal the prevalence of HPV 39 and the genetic polymorphisms of HPV39 based on E6, E7 and L1 gene in southwest China. Methods Cell samples were collected by cervical scraped for HPV detecting and typing, and HPV39 positive samples were selected out. Important E6, E7 and L1 genes of HPV39 were sequenced and analyzed for the study of HPV39 genetic polymorphisms. Phylogenetic trees were constructed by Maximum-likelihood and Kimura 2-parameters methods in Molecular Evolutionary Genetics Analysis version 6.0. The selection pressures of E6, E7 and L1 genes were estimated by Datamonkey web server. The secondary and three-dimensional structure of HPV39 E6, E7 proteins were created by sopma server and SWISS-MODEL software. Results 344 HPV39 positive samples were selected from 5718 HPV positive cell samples. Among HPV39 E6-E7 sequences, 20 single nucleotide mutations were detected, including 10 non-synonymous and 10 synonymous mutations; 26 single nucleotide mutations were detected in HPV39 L1 sequences, including 7 non-synonymous and 19 synonymous mutations respectively. 11 novel variants of HPV39 E6-E7 (5 in E6 and 6 in E7) and 14 novel variants of HPV39 L1 were identified in this study. A-branch was the most frequent HPV39 lineage in southwest China during our investigation. Selective pressure analysis showed that codon sites 26, 87, 151 in E6 and 75, 180, 222, 272, 284, 346, 356 in L1 were positively selected sites, as well as codon sites 45, 138, 309, 381 were negative selection sites in L1 gene, E7 has neither positive selection sites nor negative selection sites. A certain degree of secondary and three-dimensional structure dislocation was existed due to the non-synonymous mutations. Conclusions Amino acid substitution affected the secondary and three-dimensional structure of HPV39, and resulting in the differences of carcinogenic potential and biological functions as well as the immune response due to the antigen epitopes difference, the antigen epitopes with stronger adaptability in Southwest will be screened out based on the above research results for the later vaccine development. And gene polymorphism of HPV39 in Southwest China may improve the effectiveness of clinical test and vaccine design, specifically for women in Southwest China.

Trends in cocirculation of oncogenic HPV genotypes in single and multiple infections among the unvaccinated community

“…However, some HPV genotypes, for example, HPV53 (probably HR), HPV31 (HR), HPV51 (HR), and HPV52 (HR) were also common in various ethnicities and continents. Overall, our findings were consistent with other scientific reports but a larger sample size of population study, genotyping with an approved diagnostic assay, and sequencing were advantages of the study 29,31,34,35,45–48 …”

“…However, some HPV genotypes, for example, HPV53 (probably HR), HPV31 (HR), HPV51 (HR), and HPV52 (HR) were also common in various ethnicities and continents. Overall, our findings were consistent with other scientific reports but a larger sample size of population study, genotyping with an approved diagnostic assay, and sequencing were advantages of the study 29,31,34,35,[45][46][47][48]. F I G U R E 4 Phylogenetic tree constructed from the L1 (major capsid protein) nucleotide sequence of the isolated low-risk HPVs 6 and 11 genotypes from Iran and reference HPV genotypes.…”

E6/E7 Oncogenes Mutation of Human Papillomavirus Type 16 Associated with P16 Protein Expression in Cervical Cancer

“…E7 oncogene mutations are located in the N29S, N29T, R77C and S95S amino acids which are outside the pRB binding site region, proving that the N29S, N29H and R77S variants have lower E7 levels in cells compared to wild type E7 and impaired amino acid residues. proximity to the LxCxE (aa 22-26), CK II (aa 31-32) and CxxC (aa 58-61 and aa 91-94) regions can disrupt the structure of E7 and reduce its oncogenic potential [25]. While the E6 mutation in this study was dominated by non-synonymous mutations that did not cause changes in amino acids and did not change the function of the protein at the codon so that it did not have the potential to change the oncogenic potential of E6, in contrast to previous studies which had non-synonymous mutation variants in Q14H, H78Y and L83V which has a higher oncogenic potential and has a higher p16 level than other variants [26]- [29].…”

Association Between E6 and E7 Human Papilloma Virus Type 16 Oncogen Mutations and P21 Protein Expression in Cervical Cancer

“…This is also the constraint in a study where several fresh samples and samples have been Preserved in paraffin before being sent together for analysis. Limitations potential other is lack of analysis continuity live, so fail to determine score prognostic HPV infection and regulatory proteins cycle cells/apoptosis [24].…”