Clinical and molecular pathogenesis of varicella virus infection.
Varicella zoster virus (VZV) is a neurotropic human herpesvirus that infects nearly all humans and causes chickenpox (varicella). After chickenpox, VZV becomes latent in cranial nerve, dorsal root, and autonomic nervous system ganglia along the entire neuraxis. Virus reactivation produces shingles (zoster), characterized by pain and rash usually restricted to 1-3 dermatomes. Zoster is often complicated by postherpetic neuralgia (PHN), pain that persists for months to years after rash resolves. Virus may also spread to the spinal cord and blood vessels of the brain, producing a unifocal or multifocal vasculopathy, particularly in immunocompromised individuals. The increased incidence of zoster in elderly and immunocompromised individuals appears to be due to a VZV-specific host immunodeficiency. PHN may reflect a chronic VZV ganglionitis, and VZV vasculopathy is due to productive virus infection in cerebral arteries. Strategies that might boost host cell-mediated immunity to VZV are discussed, as well as the physical state of viral nucleic acid during latency and the possible mechanisms by which herpesvirus latency is maintained and virus is reactivated. A current summary of varicella latency and pathogenesis produced by simian varicella virus (SVV), the counterpart of human VZV, points to the usefulness of a primate model of natural infection to study varicella latency, as well as the experimental model of intratracheal inoculation to study the effectiveness of antiviral agents in driving persistent varicella virus into a latent state.
Department of Neurology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. don.gilden@uchsc.edu
Donald H
DH
Gilden
Randall J
RJ
Cohrs
Ravi
R
Mahalingam
D000818:Animals; D002644:Chickenpox / Q000209:etiology* / Q000276:immunology / Q000821:virology; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D004195:Disease Models, Animal; D005724:Ganglia / Q000821:virology; D016679:Genome, Viral; D000882:Haplorhini; D014645:Herpesvirus 3, Human / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D006801:Humans; D007111:Immunity, Cellular; D007114:Immunization; D016867:Immunocompromised Host
D004279:DNA, Viral