Phylogenetic analysis of varicella-zoster virus: evidence of intercontinental spread of genotypes and recombination

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.

FIG. 1.

Alignment of nucleotide polymorphisms in strains of VZV from around the world. The country of origin of the virus is shown in the first column (Netherlnd, The Netherlands; G. Bissau, Guinea Bissau; B'desh, Bangladesh; S. India, South India; UK, United Kingdom). The regions which contained SNPs among the original 10 United Kingdom viruses typed are shown. Shaded boxes represent ORFs in which nucleotide changes were nonsynonymous. Regions within ORFs 1, 21, 50, and 54 which show fixed differences between genotypes were used to type additional strains from the United Kingdom and around the world; ▸ indicates recombinant virus. Letters A, B, and C refer to different genotypes as defined by phylogenetic analysis (see Fig. 2). Virus originating in the United Kingdom (blue), Brazil (brown), Zambia or Guinea Bissau (orange), South India or Bangladesh (yellow), and Japan (magenta) are shown.

FIG. 2.

Phylogenetic tree of varicella-zoster virus strains by the neighbor-joining method. The countries from which specimens were obtained are shown: Bang, Bangladesh; Brasil, Brazil; Jap, Japan; GB, Guinea Bissau; Neth, The Netherlands; Sind, South India; ZAMB, Zambia. Bootstrap values separating clades A, B, and C are shown. + denotes additional viruses with identical sequence.