Genetic Change of Varicella-Zoster Virus Propagated in Cell Culture in Non-Natural Conditions

Abstract

ƒThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ license/by-nc/3.0/). Primary infection of varicella-zoster virus (VZV) causes varicella and often leads to zoster after reactivation from latency. Both varicella and zoster can be prevented by live attenuated vaccines, but the molecular mechanism of attenuation is not clearly understood. In this study, it was attempted to understand mechanism of attenuating mutation in VZV by in vitro propagation in non-natural conditions such as low temperature or non-human cell. Clinical strain YC02 was subcultured in vitro up to 60 times. Comparison of the genome sequences of YC02 variants cultured under various conditions identified specific mutations occurred in non-natural conditions. The mutations specific for low temperature culture and non-human cell culture were identified in 8 and 2 positions, respectively. Two vaccine-specific mutations in position 97748 and 106262 were identified during subculture in non-natural conditions. Genetic diversity as measured by genetic polymorphism and Shannon entropy decreased when cultured in guinea pig lung cell culture. The infectivity of YC02 cultured at low temperature appeared similar to that cultured in natural condition. On the other hands, infectivity decreased significantly when YC02 was subcultured in non-human cell. Further studies on mutations and genetic diversity of clinical strain cultured in non-natural conditions will help to elucidate the molecular mechanism of VZV attenuation.