title: An animal model of varicella virus infection.
abstract: Varicella-zoster virus (VZV) causes chickenpox in children; establishes latency in cranial nerve, dorsal root, and autonomic ganglia; and reactivates decades later to produce zoster. VZV produces disease only in humans. Although attempts to produce disease and study VZV latency in experimentally infected animals have resulted in virus in trigeminal or dorsal root ganglia, no clinical signs of infection or reactivation developed. In contrast, simian varicella virus (SVV) produces a naturally occurring exanthematous disease in non-human primates that mimics human varicella. Experimental inoculation of non-human primates causes similar, if not identical, clinical and pathological changes observed in monkeys naturally infected with SVV. Like VZV, SVV becomes latent in ganglia and reactivates, often with entire body rash. SVV and VZV encode antigenically related polypeptides. Both virus genomes have been sequenced and shown to be colinear, sharing up to 75% DNA homology. During latency, an SVV homolog of one of the five VZV genes transcribed in latently infected human ganglia has been detected in monkey ganglia. Preliminary studies in which monkeys were inoculated intratracheally with SVV revealed the presence of viral DNA and RNA in multiple tissues, including blood mononuclear cells, months after experimental infection. These findings differed from the expected restricted localization of the virus DNA to ganglia only and the expected limited viral gene expression, and probably reflect the high virus load delivered intratracheally compared to natural SVV infection in monkeys. Nevertheless, clinical, pathological, and molecular similarities between SVV and VZV indicate that SVV infection in non-human primates has considerable potential as an animal model for human varicella.
authors.affiliation: Department of Neurology, University of Colorado Health Sciences Center, Denver 80262, USA.
authors.forename: T M
authors.initials: TM
authors.lastname: White
authors.forename: D H
authors.initials: DH
authors.lastname: Gilden
authors.forename: R
authors.initials: R
authors.lastname: Mahalingam
mesh_terms: D000818:Animals; D002644:Chickenpox / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D000882:Haplorhini / Q000821:virology*; D014645:Herpesvirus 3, Human / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D009420:Nervous System / Q000473:pathology / Q000503:physiopathology / Q000821:virology; D019562:Viral Load
chemical_list: D004279:DNA, Viral