Phylogenetic Analysis of Varicella-Zoster Virus: Evidence of Intercontinental Spread of Genotypes and Recombination

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Abstract
A heteroduplex mobility assay was used to identify variants of varicella-zoster virus circulating in the United Kingdom and elsewhere. Within the United Kingdom, 58 segregating sites were found out of the 23,266 examined (0.25%), and nucleotide diversity was estimated to be 0.00063. These are an order of magnitude smaller than comparable estimates from herpes simplex virus type 1. Sixteen substitutions were nonsynonymous, the majority of which were clustered within surface-expressed proteins. Extensive genetic correlation between widely spaced sites indicated that recombination has been rare. Phylogenetic analysis of varicella-zoster viruses from four continents distinguished at least three major genetic clades. Most geographical regions contained only one of these three strains, apart from the United Kingdom and Brazil, where two or more strains were found. There was minimal genetic differentiation (one or fewer substitutions in 1,895 bases surveyed) between the samples collected from Africa (Guinea Bissau, Zambia) and the Indian subcontinent (Bangladesh, South India), suggesting recent rapid spread and/or low mutation rates. The geographic pattern of strain distribution would favor a major influence of the former. The genetic uniformity of most virus populations makes recombination difficult to detect. However, at least one probable recombinant between two of the major strains was found among the samples originating from Brazil, where mixtures of genotypes co-occur.