Abstract
Varicella zoster virus (VZV) is a highly neurotropic, exclusively human herpesvirus. Primary infection causes varicella (chickenpox), wherein VZV replicates in multiple organs, particularly the skin. Widespread infection in vivo is confirmed by the ability of VZV to kill tissue culture cells in vitro derived from any organ. After varicella, VZV becomes latent in ganglionic neurons along the entire neuraxis. During latency, virus DNA replication stops, transcription is restricted, and no progeny virions are produced, indicating a unique virus-cell (neuron) relationship. VZV reactivation produces zoster (shingles), often complicated by serious neurological and ocular disorders. The molecular trigger(s) for reactivation, and thus the identity of a potential target to prevent it, remains unknown due to an incomplete understanding of the VZV-neuron interaction. While no in vitro system has yet recapitulated the findings in latently infected ganglia, recent studies show that VZV infection of human neurons in SCID mice and of human stem cells, including induced human pluripotent stem cells and normal human neural progenitor tissue-like assemblies, can be established in the absence of a cytopathic effect. Usefulness of these systems in discovering the mechanisms underlying reactivation awaits analyses of VZV-infected, highly pure (>90%), terminally differentiated human neurons capable of prolonged survival in vitro.
Highlights
Primary infection with varicella zoster virus (VZV), a highly neurotropic, exclusively human herpesvirus, causes varicella, during which time VZV replicates in multiple organs, the skin [1]
While no in vitro system has recapitulated findings in latently infected ganglia, recent studies indicate that VZV infection of neurons in vitro can be established in the absence of a cytopathic effect (Table 1), holding the promise of molecular analysis of virus-neuronal interactions to discover the mechanisms of virus reactivation from latency
The virus persists in ganglionic neurons for decades before reactivation, while traditional 2-dimensional neuronal cultures survive for only a few weeks, and even 3-dimensional human neuronal Tissue-Like Assemblies (TLA) can only be maintained for some months
Summary
Primary infection with varicella zoster virus (VZV), a highly neurotropic, exclusively human herpesvirus, causes varicella (chickenpox), during which time VZV replicates in multiple organs, the skin [1]. The ultimate development of a model in which VZV becomes latent in neurons, characterized by the absence of a virus-induced cytopathic effect (CPE) and limited VZV transcription will provide a system to study molecules that induce reactivation. Identification of such molecules promises to identify therapeutic targets to prevent virus reactivation, a cause of serious, sometimes fatal neurologic disease, especially in the elderly/immunocompromised populations. This review presents an overview of VZV configuration and viral gene expression in latently infected human ganglia, followed by a comparison of various model systems designed to produce an equivalent virus-host relationship in neurons in vitro
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
