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

Abstract

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...

Evidence of widespread natural recombination among field isolates of equine herpesvirus 4 but not among field isolates of equine herpesvirus 1

“…It is possible that EHV-1 recombination events may have occurred but were not able to be detected at the required level of statistical significance, because an insufficient number of SNPs specific for the parental viruses were transferred to the recombinant viruses. However, evidence of frequent, natural recombination has been readily detected in VZV, which also has a highly conserved genome (approximately 30-200 SNP differences between any two strains), using similar methods to those in this study (Norberg et al, 2015(Norberg et al, , 2006Zell et al, 2012).…”

“…Recent advances in high-throughput sequencing of complete viral genomes have allowed natural (field) recombination to be studied in a number of different alphaherpesviruses affecting animals and humans, including herpes simplex virus 1 (HSV-1), varicella-zoster virus (VZV) and infectious laryngotracheitis virus (ILTV) (Kolb et al, 2013;Lee et al, 2013;Norberg et al, 2015Norberg et al, , 2006Peters et al, 2006). Such studies provide insights into virus evolution and also allow the risk of recombination to be assessed in the context of attenuated vaccine use.…”

The Evidence of Annual Occurrence of Varicella Zoster Virus (Vzv) in Temper Climate of Czech Republic

“…SNP v těchto segmentech diferencují mezi evropským kmenem E1 a E2. Metoda byla opět popsána a publikována dříve (8). Všechna sekvenování probíhala na ABI Prism 3100 DNA sekvenátoru (Perkin-Elmer, Walthan, MA, USA) za použití BigDye Terminator v3.1.…”

“…V rámci celého VZV genomu je popsáno pouhých 0,1 % změn, projevujících se záměnou jednotlivých nukleotidových bází (SNP-single nucleotide polymorphism) (9). Pro srovnání, diversita genomu HSV-1 je oproti VZV genomu 6x vyšší (8).…”

“…Ta umožňuje herpetickým virům získat "výhodné" mutace z rodičovských genomů, a tím funkčně profitovat. Rekombinace zároveň ovlivňují hladinu virulence VZV (8,16).…”