Abstract
Varicella-zoster virus (VZV) is a human herpes virus which causes varicella (chicken pox) as a primary infection, and, following a variable period of latency in neurons in the peripheral ganglia, may reactivate to cause herpes zoster (shingles) as well as a variety of neurological syndromes. In this overview we consider some recent issues in alphaherpesvirus latency with special focus on VZV ganglionic latency. A key question is the nature and extent of viral gene transcription during viral latency. While it is known that this is highly restricted, it is only recently that the very high degree of that restriction has been clarified, with both VZV gene 63-encoded transcripts and discovery of a novel VZV transcript (VLT) that maps antisense to the viral transactivator gene 61. It has also emerged in recent years that there is significant epigenetic regulation of VZV gene transcription, and the mechanisms underlying this are complex and being unraveled. The last few years has also seen an increased interest in the immunological aspects of VZV latency and reactivation, in particular from the perspective of inborn errors of host immunity that predispose to different VZV reactivation syndromes.
Highlights
latency associated transcript (LAT) transcription begins in the internal repeat of the unique long segment, but since this 9212 base pair region in herpes simplex virus-1 (HSV-1) is only 88 bp in Varicella-zoster virus (VZV), varicella latency transcript (VLT) transcription begins within the unique long segment of the virus DNA
The complex interplay between histone posttranslational modifications (PTM) is seen during early-stage virus reactivation when multiple HSV-1 [69,70,71,72] and VZV [20,22,73,74,75] genes of all kinetic classes are transcribed independent of preexisting virus transcription factors
During the last decade there has been a significant increase in our detailed knowledge of the complex mechanism underlying VZV latency, as well as an emerging appreciation of the diversity of the clinical syndromes caused by VZV reactivation
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. After a variable period, which can span several decades, VZV may reactivate from the latent state in human ganglia to cause the well-recognised syndrome of herpes zoster (shingles) which is an extremely painful vesicular rash with an anatomical distribution of a particular sensory dermatome [3]. Because of the limitations of studying viral latency in post-mortem tissues (see below), future studies might rely on induced pluripotent stem cells and/or neuronal or brain organoids [9]. In this overview, the intention is to highlight some recent developments in our thinking about alphaherpesvirus latency, and VZV in particular; this review will be selective rather than comprehensive. But related, aspects of VZV latency will be considered, namely viral gene expression in latently infected ganglia, epigenetic control of viral transcription and immunological aspects of VZV latency and reactivation, the latter mainly based on studies of patients with severe VZV infection and underlying inborn errors of immunity
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