Key issues in varicella-zoster virus latency.

Abstract

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.