Abstract
Varicella-zoster virus (VZV) causes chickenpox in children and shingles in older people. Currently, live attenuated vaccines based on the Oka strain are available worldwide. In Korea, an attenuated VZV vaccine has been developed from a Korean isolate and has been commercially available since 1994. Despite this long history of use, the mechanism for the attenuation of the vaccine strain is still elusive. We attempted to understand the molecular basis of attenuation mechanism by full genome sequencing and comparative genomic analyses of the Korean vaccine strain SuduVax. SuduVax was found to contain a genome that was 124,759 bp and possessed 74 open reading frames (ORFs). SuduVax was genetically most close to Oka strains and these Korean-Japanese strains formed a strong clade in phylogenetic trees. SuduVax, similar to the Oka vaccine strains, underwent T- > C substitution at the stop codon of ORF0, resulting in a read-through mutation to code for an extended form of ORF0 protein. SuduVax also shared certain deletion and insertion mutations in ORFs 17, 29, 56 and 60 with Oka vaccine strains and some clinical strains. The Korean VZV vaccine strain SuduVax is genetically similar to the Oka vaccine strains. Further comparative genomic and bioinformatics analyses will help to elucidate the molecular basis of the attenuation of the VZV vaccine strains.
Highlights
Varicella-zoster virus (VZV) causes chickenpox in children and shingles in older people
The architecture of the SuduVax genome is typical of VZV in that the genome could be divided into TRL, UL, IRL, IRS, US and TRS (88, 104,799, 88, 7,276, 5,232, and 7276 bp, respectively)
The lengths of the genome, lengths of each region and the G + C contents are very similar among the 24 VZV strains analyzed in this study (Table 1)
Summary
Overall genome structure of the Korean vaccine strain SuduVax The genome of the VZV strain SuduVax was determined to be 124,759 bp. As shown in an unrooted tree generated by maximum-likelihood method, SuduVax and four Oka strains (pOka, vOka, VarilRix, VariVax) formed a clade and strains M2DR and 8 formed an adjacent clade (Figure 2a). These two clades were joined with the clade whose member was the strain CA123 only. Four vaccine strains (vOka, VarilRix, VariVax, and SuduVax) formed a subclade within the clade 2 in the trees built by full or coding sequences (bootstrap value = 1,000 in neighbour-joining trees), but not in the tree built by non-coding sequences. The same read-through mutation was found in other vaccine strains, vOka, VarilRix and VariVax. All clinical strains including pOka contained 390 bp-long ORF0 coding for 129 amino acids.
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