Evolution and world-wide distribution of varicella-zoster virus clades

Varicella-zoster virus (VZV, Human herpesvirus 3), a world-wide distributed pathogen, is the causative agent of varicella (chickenpox) and zoster (shingles). Both diseases result in significant morbidity and economic burden. The implementation of routine varicella vaccination programs in many countries may reduce significantly the incidence of varicella disease. Furthermore, vaccination against zoster can diminish the burden of zoster considerably. Although many epidemiological, clinical and laboratory studies were performed in the past decades to reveal the clinical burden as well as epidemiological features and changes of the two diseases caused by VZV, a comparatively low number of molecular epidemiological studies have been performed to investigate and monitor the genetic variability and phylogenetic relationship of VZV strains throughout the world. To date, it is well established that VZV can be divided into five major clades confirmed by full-genome sequencing and two provisional clades that have to be confirmed. Additionally, several studies have demonstrated a regional dominance of specific VZV clades, most likely in dependence on environmental factors, evolutionary conditions and host-virus interactions and/or importation of viral strains. However, there are many open questions such as the alteration of genotype distribution through immigration or travel, the introduction of the varicella vaccine strain into population and the emergence of wild-type vaccine recombinant viruses. To increase our knowledge in this field by further innovative approaches, the new common nomenclature of VZV clades established recently will be very useful. In this review, the currently available data concerning the geographic distribution and evolution of VZV clades are summarized. Different models of VZV evolution and recombination are discussed and recent changes in VZV clade distribution addressed.