Vaccine-type mutations identified in Varicella zoster virus passaged in cell culture

Virus Res. 2018 Feb 2:245:62-68. doi: 10.1016/j.virusres.2017.12.004. Epub 2017 Dec 12.

Abstract

Varicella-zoster virus (VZV) is a causative agent for chickenpox and shingles. Comparative genomic sequence analysis of clinical and vaccine strains suggested potential sites responsible for attenuation. In this study, low and high passages of two VZV clinical strains cultured in human fibroblast cells were compared for genomic DNA sequences and growth characteristics. Mutations were detected at 187 and 162 sites in the strain YC01 and YC02, respectively. More than 86% of mutations were found in open reading frames, and ORF62 exhibited highest frequency of mutations. T to C and A to G transitions accounted for more 90% of all possible substitutions. Forty mutations were common to two strains, including 27 in ORF62. Mutations found in attenuated vaccine strains were also detected at 7 positions. Both high and low passage strains were infectious and grew similarly in human fibroblast cells. In guinea pig cells, however, high passage strain remained infectious while low passage strain lost infectivity. This study may provide new insight into the attenuating mutations associated with in vitro passaging of VZV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Culture Techniques
  • Cell Line
  • Chickenpox Vaccine / genetics*
  • Chickenpox Vaccine / immunology
  • Fibroblasts / immunology
  • Fibroblasts / virology*
  • Foreskin / cytology
  • Gene Expression
  • Guinea Pigs
  • Herpesvirus 3, Human / genetics*
  • Herpesvirus 3, Human / growth & development
  • Herpesvirus 3, Human / immunology
  • Host Specificity
  • Humans
  • Immediate-Early Proteins / genetics*
  • Immediate-Early Proteins / immunology
  • Lung / cytology
  • Male
  • Open Reading Frames
  • Point Mutation*
  • Trans-Activators / genetics*
  • Trans-Activators / immunology
  • Vaccines, Attenuated
  • Viral Envelope Proteins / genetics*
  • Viral Envelope Proteins / immunology

Substances

  • Chickenpox Vaccine
  • IE62 protein, Human herpesvirus 3
  • Immediate-Early Proteins
  • Trans-Activators
  • Vaccines, Attenuated
  • Viral Envelope Proteins