A comparison of herpes simplex virus type 1 and varicella-zoster virus latency and reactivation

Kennedy, P. G.E., Rovnak, J., Badani, H. and Cohrs, R. J. (2015) A comparison of herpes simplex virus type 1 and varicella-zoster virus latency and reactivation. Journal of General Virology, 96, pp. 1581-1602. (doi: 10.1099/vir.0.000128) (PMID:25794504)

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Abstract

Herpes simplex virus type 1 (HSV-1) and varicella zoster virus (VZV) are human neurotropic alphaherpesviruses that cause lifelong infections in ganglia. Following primary infection and establishment of latency, HSV-1 reactivation typically results in herpes labialis (cold sores), but can occur frequently elsewhere on the body at the site of primary infection (e.g. whitlow), particularly at the genitals. Rarely, HSV-1 reactivation can cause encephalitis; however, 1/3 of the cases of HSV-1 encephalitis are associated with HSV-1 primary infection (Whitley & Gnann, 2002). Primary VZV infection causes varicella (chickenpox) following which latent virus may reactivate decades later to produce herpes zoster (shingles), as well as an increasingly recognized number of subacute, acute and chronic neurological conditions. Following primary infection, both viruses establish a latent infection in neuronal cells in human peripheral ganglia. However, the detailed mechanisms of viral latency and reactivation have yet to be unraveled. In both cases latent viral DNA exists in an "end-less" state where the ends of the virus genome are joined to form structures consistent with unit length episomes and concatemers, from which viral gene transcription is restricted. In latently infected ganglia, the most abundantly detected HSV-1 RNAs are the spliced products originating from the primary Latency Associated Transcript (LAT). This primary LAT is an 8.3 kb unstable transcript from which two stable (1.5 and 2.0 kb) introns are spliced. Transcripts mapping to 12 VZV genes have been detected in human ganglia removed at autopsy; however, it is difficult to ascribe these as transcripts present during latent infection since early stage virus reactivation may have transpired in the post mortem time period in the ganglia. Nonetheless, low-level transcription of VZV gene 63 has been repeatedly detected in multiple ganglia removed as close to death as possible. There is increasing evidence that HSV-1 and VZV latency is epigenetically regulated. In vitro models that permit pathway analysis and identification of both epigenetic modulations and global transcriptional mechanisms of HSV-1 and VZV latency hold much promise for our future understanding in this complex area. This review summarizes the molecular biology of HSV-1 and VZV latency and reactivation as well as presents future directions for study.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Kennedy, Professor Peter
Authors: Kennedy, P. G.E., Rovnak, J., Badani, H., and Cohrs, R. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of General Virology
Publisher:Society for General Microbiology
ISSN:0022-1317
ISSN (Online):1465-2099

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