Recombination in tissue culture between varicella‐zoster virus strains

136

103

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 varicellazoster 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.

Section: Discussionmentioning

confidence: 93%

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

Muir

Nichols

Breuer

2002

136

103

“…It has been reported that coinfection with two different strains of the same herpesvirus led to the production of recombinant viruses both in vitro and in vivo (14,20,21,25,49,51). To quantify the recombination between the two parental BoHV-1 used in the present study, MDBK cells were coinfected with both Lam gC…”

Section: Resultsmentioning

confidence: 99%

Superinfection Prevents Recombination of the Alphaherpesvirus Bovine Herpesvirus 1

Meurens¹,

Schynts

Keil

et al. 2004

Homologous recombination between strains of the same alphaherpesvirus species occurs frequently both in vitro and in vivo. This process has been described between strains of herpes simplex virus type 1, herpes simplex virus type 2, pseudorabies virus, feline herpesvirus 1, varicella-zoster virus, and bovine herpesvirus 1 (BoHV-1). In vivo, the rise of recombinant viruses can be modulated by different factors, such as the dose of the inoculated viruses, the distance between inoculation sites, the time interval between inoculation of the first and the second virus, and the genes in which the mutations are located. The effect of the time interval between infections with two distinguishable BoHV-1 on recombination was studied in three ways: (i) recombination at the level of progeny viruses, (ii) interference induced by the first virus infection on ␤-galactosidase gene expression of a superinfecting virus, and (iii) recombination at the level of concatemeric DNA. A time interval of 2 to 8 h between two successive infections allows the establishment of a barrier, which reduces or prevents any successful superinfection needed to generate recombinant viruses. The dramatic effect of the time interval on the rise of recombinant viruses is particularly important for the risk assessment of recombination between glycoprotein E-negative marker vaccine and field strains that could threaten BoHV-1 control and eradication programs.

“…Recombination between different VZV strains has been described in cell culture using restriction endonuclease fragment size analysis and hybridization (9). DNA sequence and singlenucleotide polymorphism analyses have been used to detect probable recombination in several few clinical VZV isolates (30,44), and homologous recombination has also been documented in other herpesviruses.…”

Section: Discussionmentioning

confidence: 99%

Complete-Genome Phylogenetic Approach to Varicella-Zoster Virus Evolution: Genetic Divergence and Evidence for Recombination

Norberg

Liljeqvist

Bergström

et al. 2006

Recent studies of varicella-zoster virus (VZV) DNA sequence variation, involving large numbers of globally distributed clinical isolates, suggest that this virus has diverged into at least three distinct genotypes designated European (E), Japanese (J), and mosaic (M). In the present study, we determined and analyzed the complete genomic sequences of two M VZV strains and compared them to the sequences of three E strains and two J strains retrieved from GenBank (including the Oka vaccine preparation, V-Oka). Except for a few polymorphic tandem repeat regions, the whole genome, representing approximately 125,000 nucleotides, is highly conserved, presenting a genetic similarity between the E and J genotypes of approximately 99.85%. These analyses revealed that VZV strains distinctly segregate into at least four genotypes (E, J, M1, and M2) in phylogenetic trees supported by high bootstrap values. Separate analyses of informative sites revealed that the tree topology was dependent on the region of the VZV genome used to determine the phylogeny; collectively, these results indicate the observed strain variation is likely to have resulted, at least in part, from interstrain recombination. Recombination analyses suggest that strains belonging to the M1 and M2 genotypes are mosaic recombinant strains that originated from ancestral isolates belonging to the E and J genotypes through recombination on multiple occasions. Furthermore, evidence of more recent recombination events between M1 and M2 strains is present in six segments of the VZV genome. As such, interstrain recombination in dually infected cells seems to figure prominently in the evolutionary history of VZV, a feature it has in common with other herpesviruses. In addition, we report here six novel genomic targets located in open reading frames 51 to 58 suitable for genotyping of clinical VZV isolates.In temperate climates, varicella-zoster virus (VZV) is a ubiquitous human pathogen with tropism to skin and sensory ganglia. VZV establishes latent infections, most prominently in the dorsal root and trigeminal ganglia, resulting in a permanent association with the host that may reactivate many decades after primary infection to cause herpes zoster. Primary VZV infection is nearly always symptomatic (varicella), a normally benign childhood disease; occasionally first exposure results in more serious illness or, in rare instances, death (40). Several neurological manifestations have been described in relation to VZV reactivation, such as facial palsy, encephalitis, meningitis, and cerebral vasculitis, conditions that may occur without any dermal lesions (4, 12, 16). The combined disease burden of primary and reactivated VZV infections has motivated widespread vaccination using a live, attenuated VZV strain (V-Oka). More recently, it has been demonstrated that a high-dose formulation of V-Oka can prevent or substantially ameliorate both herpes zoster and postherpetic neuralgia in persons 60 years of age and older (33).The genetic diversity of various human herpesviru...