Distribution of varicella-zoster virus (VZV) wild-type genotypes in northern and southern Europe: Evidence for high conservation of circulating genotypes

Abstract

Phylogenetic analysis of 19 complete VZV genomic sequences resolves wild-type strains into 5 genotypes (E1, E2, J, M1, and M2). Complete sequences for M3 and M4 strains are unavailable, but targeted analyses of representative strains suggest they are stable, circulating VZV genotypes. Sequence analysis of VZV isolates identified both shared and specific markers for every genotype and validated a unified VZV genotyping strategy. Despite high genotype diversity no evidence for intra-genotypic recombination was observed. Five of seven VZV genotypes were reliably discriminated using only four single nucleotide polymorphisms (SNP) present in ORF22, and the E1 and E2 genotypes were resolved using SNP located in ORF21, ORF22 or ORF50. Sequence analysis of 342 clinical varicella and zoster specimens from 18 European countries identified the following distribution of VZV genotypes: E1, 221 (65%); E2, 87 (25%); M1, 20 (6%); M2, 3 (1%); M4, 11 (3%). No M3 or J strains were observed.

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“…8 ) plus variation in targeted SNPs in either ORF 21 or ORF 50 (ref. 8,9 ) categorized VZV wild-type strains to different wild-type genotypes of VZV (ref. 9) .…”

“…PCR amplifications of the ORF21 -502 bp target region, ORF22 -447 bp target region, ORF50 -514 bp target region were performed with a GeneAmp PCR System 9700 (Applied Biosystems, Carlsbad, CA) using 5 μl of DNA extracted from skin lesions of the patient. PCR products were separated on 4% precast gradient polyacrylamide gels prestained with ethidium bromide (Invitrogen) and visualized under UV irradiation alongside a 100-bp ladder (Invitrogen) [7][8][9]11,12 . Similar methods were used for multi-locus DNA sequence analysis at ORF 1,6, 9 and 28.…”

“…All genomic loci refer to the published sequence for the Dumas strain (Genbank accession #9625875). The sequences of primers and probes were described and published previously [6][7][8][9]11,12 . Automated DNA sequencing was performed using the Genomelab GeXP (Beckman Coulter, Fullerton, CA) according to the manufacturer's instructions.…”

“…Several studies have demonstrated a distinctive geographic distribution of the major VZV genotypes aligning with cool versus warm climate regions of the globe 6 . It is unclear whether the strain distribution is actually driven by climate or/and other factors, such as immigration patterns [7][8][9] .…”

“…The E genotypes are the most prevalent genotype in the United States, Canada, Europe, and eastern Australia. The J genotype is typically found in Japan and Asia.The M genotypes are prevalent mostly in tropical countries, including Panama, Costa Rica, Barbados, Sudan, New Zealand, western part of Australia [7][8][9] .…”