Journal of Antivirals & Antiretrovirals
Open Access

Abstract

Newly Developed Approaches for Studying Pathogenesis of Varicella Zoster Virus

Benjamin Silver, Vivianna Lin and Hua Zhu

Varicella-zoster virus (VZV) is a herpesvirus that is the causative agent of chickenpox and herpes zoster. The virus manifests as chickenpox upon primary infection, establishes latency in the sensory neurons, and can later reactivate as herpes zoster when the immune system is compromised. Although the v-Oka vaccine has been introduced to most children worldwide, the virus remains neurovirulent and is thus still able to reactivate and cause herpes zoster. Knowledge about VZV pathogenesis has been limited due to its highly cell-associated nature in culture, difficulty in generating recombinant viruses, and obstacles in in vivo viral pathogenesis studies. However, a combination of new approaches has made it possible to functionally profile the entire VZV genome, screen for tissue tropic factors, and analyze recombinant virus replication and pathogenesis in vivo. These approaches include the bacterial artificial chromosome technology for generating recombinant VZV, the humanized mouse model for studying viral tropism and pathogenesis in vivo, and a bioluminescence marker for monitoring viral growth in all models. From these recombinant virus studies, open reading frame 7 of the VZV genome was revealed to be a novel skin- and neurotropic factor. In addition, studies of the closely related Simian Varicella Virus and other VZV pathogenic studies in conjunction with genetic analyses of the entire VZV genome will not only lead to a better understanding of VZV pathogenesis, but also contribute to the development of a safer, more effective neuroattenuated vaccine candidate.