Recent Issues in Varicella-Zoster Virus Latency

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.

Keywords: epigenetics; gene expression; immunity; latency; neuron; reactivation; varicella-zoster; virus.

Figure 1

Latency associated transcription regions of VZV and HSV-1. The regions of VZV (top panel) and HSV-1 (bottom panel) that span predicted (VZV) or discovered (HSV-1) CTCF-binding sites are shown relative to the most current VZV transcription annotation (Braspenning et al. 2020) and the annotated HSV-1 reference sequence (NCBI Reference Sequence: NC_001806.2). The genomes are presented with the latency associated transcripts on the top strand in 5’ to 3’ orientation. Arrows show the relative size and direction of each transcript with exons (thick arrows/lines) and introns (thin lines). The red colored latency associated transcripts are distinguished from the blue lytic gene transcripts with the VZV Varicella Latency Transcripts associated with initial stage of virus reactivation colored green (VLTlyt). Specific genes mentioned in the text are identified by number (VZV) or name (HSV-1) with variants of associated genes contained within boxes. The topological architecture of each genome is shown in yellow boxes with the unique long (UL), unique short (US) and associated repeat regions (ULR, USR) highlighted. The nucleotide position of the selected DNA regions is listed for each virus in the ruler at the bottom of each box.