Varicella zoster virus latency, neurological disease and experimental models: an update.
Varicella zoster virus (VZV), a ubiquitous neurotropic human herpesvirus, causes chickenpox (varicella) and then remains latent for decades in cranial nerve, dorsal root and autonomic nervous system ganglia along the entire neuraxis. Virus reactivation, most often after age 60, produces shingles (zoster), characterized by pain and rash usually restricted to 1-3 dermatomes. In elderly individuals, zoster is frequently complicated by postherpetic neuralgia (PHN), pain that persists for months to years after the resolution of rash. Virus may also spread beyond ganglia to the spinal cord to cause myelitis, as well as to blood vessels of the brain, producing a unifocal or multifocal vasculopathy. The increased incidence of zoster in the elderly and immunocompromised individuals appears to be due to a VZV-specific host immunodeficiency. Recent studies indicate that PHN may be due to a chronic active VZV ganglionitis, and that VZV vasculopathy is caused by a productive virus infection in cerebral arteries. Since neurological disease produced by VZV is due to reactivation from ganglia, the physical state of viral nucleic acid and expression during latency as well as the possible mechanisms by which VZV latency is maintained and reactivates are discussed. Finally, VZV is an exclusively human herpesvirus, and experimental infection of animals with VZV does not produce disease nor does VZV reactivate from ganglia. Two varicella models in primates have proven useful: one that mimics varicella latency in humans, and one that can be used to study the efficacy of antiviral agent in driving varicella virus back to a latent state.
Cohrs
Randall J
RJ
Department of Neurology, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
Gilden
Donald H
DH
Mahalingam
Ravi
R
D000818:Animals; D002644:Chickenpox / Q000503:physiopathology* / Q000821:virology; D004195:Disease Models, Animal; D014645:Herpesvirus 3, Human / Q000502:physiology*; D006801:Humans; D008962:Models, Theoretical; D009422:Nervous System Diseases / Q000821:virology*; D009437:Neuralgia / Q000209:etiology; D017735:Virus Latency