Phylogenetic analysis of human papillomavirus proteins

Abstract

Objectives Human papillomaviruses (HPVs) have evolved over millions of years, with over 200 serotypes already identified. HPVs cause oral, cervical, and any other keratinocyte cancers and are of 2 groups based on the risk of carcinogenesis; high-risk and low-risk HPVs. Differences in the evolution of high-risk and low-risk HPVs and their association with carcinogenesis in accordance with each protein expressed by HPVs are unclear. To reduce oral carcinogenesis by HPVs, information regarding evolutionary changes in HPV proteins and the mechanism underlying the acquisition of the ability for oral carcinogenesis of HPVs is needed. This study aimed to evaluate the carcinogenic potential of HPVs via phylogenetic analysis of HPVs proteins. Study Design Eight proteins of alpha HPVs were selected, namely, E1, E2, E4, E5, E6, E7, L1, and L2. The complete amino acid sequences of these 8 HPV proteins were downloaded from the UniProtKB database. HPVs were classified into 2 groups on the basis of high or low clinical risk for cancer in accordance with the International Committee on Taxonomy of Viruses (ICTV). Phylogenetic analysis of HPV genomes was performed by using Molecular Evolutionary Genetics Analysis version 7 (MEGA7) and the neighbor-joining algorithm. Bootstrap analysis of 1000 replicates was performed on each tree to determine the confidence levels. Fisher's exact test was performed for statistical analysis, with P Results Each protein from different HPV strains consistently showed evolutionary divergence into distinct lineages. Multiple sequence alignment revealed amino acid profiles showing conserved independent lineage specific substitutions. Phylogenetic analysis revealed that HPV proteins evolved in a similar manner. Conclusions The present results provide an overview of the characteristics of HPV proteins and their evolutionary changes, potentially explaining the pathogenesis of oral cancer caused by HPVs.