Genetic variability in L1 and L2 genes of HPV-16 and HPV-58 in Southwest China

PLoS One. 2013;8(1):e55204. doi: 10.1371/journal.pone.0055204. Epub 2013 Jan 25.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Capsid Proteins / chemistry
  • Capsid Proteins / genetics*
  • China
  • Female
  • Genetic Variation*
  • Human papillomavirus 16 / genetics
  • Humans
  • Molecular Sequence Data
  • Mutation
  • Oncogene Proteins, Viral / chemistry
  • Oncogene Proteins, Viral / genetics
  • Papillomaviridae / classification
  • Papillomaviridae / genetics*
  • Papillomaviridae / isolation & purification
  • Papillomavirus Infections / virology
  • Phylogeny

Substances

  • Capsid Proteins
  • HPV L1 protein, Human papillomavirus
  • Oncogene Proteins, Viral

Associated data

  • GENBANK/JX313693
  • GENBANK/JX313694
  • GENBANK/JX313695
  • GENBANK/JX313696
  • GENBANK/JX313697
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Grants and funding

This research was supported by the National Natural Science Foundation of China (grant no. 81171946), the Natural Science Foundation of Yunnan Province (grant no. 2009ZC187M and grant no. 2011CA016), the Special Research Fund for the Doctoral Program of Higher Education of China (grant no. 20111106120055) and the Scientific Research Foundation for Returned Overseas Chinese Scholars, Ministry of Education of China. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.