Molecular Characterization of Varicella Zoster Virus in Latently Infected Human Ganglia: Physical State and Abundance of VZV DNA, Quantitation of Viral Transcripts and Detection of VZV-Specific Proteins

Abstract

Varicella zoster virus (VZV) establishes latency in neurons of human peripheral ganglia where the virus genome is most likely maintained as a circular episome bound to histones. There is considerable variability among individuals in the number of latent VZV DNA copies. The VZV DNA burden does not appear to exceed that of herpes simplex type 1 (HSV-1). Expression of VZV genes during latency is highly restricted and is regulated epigenetically. Of the VZV open reading frames (ORFs) that have been analyzed for transcription during latency using cDNA sequencing, only ORFs 21, 29, 62, 63, and 66 have been detected. VZV ORF 63 is the most frequently and abundantly transcribed VZV gene detected in human ganglia during latency, suggesting a critical role for this gene in maintaining the latent state and perhaps the early stages of virus reactivation. The inconsistent detection and low abundance of other VZV transcripts suggest that these genes play secondary roles in latency or possibly reflect a subpopulation of neurons undergoing VZV reactivation. New technologies, such as GeXPS multiplex PCR, have the sensitivity to detect multiple low abundance transcripts and thus provide a means to elucidate the entire VZV transcriptome during latency.