Analysis of single nucleotide polymorphism among Varicella-Zoster Virus and identification of vaccine-specific sites

Virology. 2016 Sep:496:277-286. doi: 10.1016/j.virol.2016.06.017. Epub 2016 Jul 1.

Abstract

Varicella-zoster virus (VZV) is a causative agent for chickenpox and zoster. Live attenuated vaccines have been developed based on Oka and MAV/06 strains. In order to understand the molecular mechanisms of attenuation, complete genome sequences of vaccine and wild-type strains were compared and single nucleotide polymorphism (SNP) was analyzed. ORF22 and ORF62 contained the highest number of SNPs. The detailed analysis of the SNPs suggested 24 potential vaccine-specific sites. All the mutational events found in vaccine-specific sites were transitional, and most of them were substitution of AT to GC pair. Interestingly, 18 of the vaccine-specific sites of the vaccine strains appeared to be genetically heterogeneous. The probability of a single genome of vaccine strain to contain all 24 vaccine-type sequences was calculated to be less than 4%. The average codon adaptation index (CAI) value of the vaccine strains was significantly lower than the CAI value of the clinical strains.

Keywords: Genetic heterogeneity; Live attenuated vaccine; Sequence diversity; Single nucleotide polymorphism (SNP); Vaccine-specific sites; Varicella-zoster virus (VZV).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Biological
  • Amino Acid Substitution
  • Chickenpox / immunology
  • Chickenpox / prevention & control
  • Chickenpox Vaccine / immunology*
  • Codon
  • Epitopes / genetics*
  • Epitopes / immunology*
  • Genome, Viral*
  • Herpesvirus 3, Human / classification
  • Herpesvirus 3, Human / genetics*
  • Herpesvirus 3, Human / immunology*
  • Humans
  • INDEL Mutation
  • Mutation
  • Open Reading Frames
  • Polymorphism, Single Nucleotide*
  • Sequence Analysis, DNA

Substances

  • Chickenpox Vaccine
  • Codon
  • Epitopes