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The molecular mechanisms by which varicella-zoster virus (VZV) causes a latent infection in human trigeminal and spinal ganglia are not well understood. It is known that VZV establishes latency in ganglia following the primary infection causing varicella (chickenpox), and that the virus may reactivate after years of dormancy to produce herpes zoster (shingles). Two key issues have been the cell-type localization of latent VZV in human ganglia, and the nature and extent of VZV gene expression during latency. Although the cell specificity of latent VZV has been controversial for almost a decade, it is now widely accepted that the virus is mainly latent in neuronal cells, with only a small proportion of non-neuronal cells infected. All of the studies carried out so far have indicated that VZV gene expression is highly restricted during ganglionic latency. Although at least four VZV genes have been identified as being expressed, the possibility that latent gene expression is significantly greater than this cannot yet be excluded. There is also evidence for VZV gene–encoded proteins being expressed during latency, although the precise extent of this is unclear. Advances in this difficult field may be expected to arise from both newly developed molecular technology and more refined animal models of VZV latency. [ABSTRACT FROM AUTHOR]

Varicella-zoster virus (VZV) is a ubiquitous human herpes virus typically acquired in childhood when it causes varicella (chickenpox), following which the virus establishes a latent infection in trigeminal and dorsal root ganglia that lasts for the life of the individual. VZV subsequently reactivates, spontaneously or after specific triggering factors, to cause herpes zoster (shingles), which may be complicated by postherpetic neuralgia and several other neurological complications including vasculopathy. Our understanding of VZV latency lags behind our knowledge of herpes simplex virus type 1 (HSV-1) latency primarily due to the difficulty in propagating the virus to high titers in a cell-free state, and the lack of a suitable small-animal model for studying virus latency and reactivation. It is now established beyond doubt that latent VZV is predominantly located in human ganglionic neurons. Virus gene transcription during latency is epigenetically regulated, and appears to be restricted to expression of at least six genes, with expression of gene 63 being the hallmark of latency. However, viral gene transcription may be more extensive than previously thought. There is also evidence for several VZV genes being expressed at the protein level, including VZV gene 63-encoded protein, but recent evidence suggests that this may not be a common event. The nature and extent of the chronic inflammatory response in latently infected ganglia is also of current interest. There remain several questions concerning the VZV latency process that still need to be resolved unambiguously and it is likely that this will require the use of newly developed molecular technologies, such as GeXPS multiplex polymerase chain reaction (PCR) for virus transcriptional analysis and ChIP-seq to study the epigenetic of latent virus genome ( Liu et al, 2010 , BMC Biol 8: 56).