title: Neuronal changes induced by Varicella Zoster Virus in a rat model of postherpetic neuralgia.
abstract: A significant fraction of patients with herpes zoster, caused by Varicella Zoster Virus (VZV), experience chronic pain termed postherpetic neuralgia (PHN). VZV-inoculated rats develop prolonged nocifensive behaviors and serve as a model of PHN. We demonstrate that primary rat cultures show a post-entry block for VZV replication, suggesting the rat is not fully permissive. However, footpads of VZV infected animals show reduced peripheral innervation and innervating dorsal root ganglia (DRG) contained VZV DNA and transcripts of candidate immediate early and early genes. The VZV-infected DRG showed changes in host gene expression patterns, with 84 up-regulated and 116 down-regulated genes seen in gene array studies. qRT-PCR validated the modulation of nociception-associated genes Ntrk2, Trpv1, and Calca (CGRP). The data suggests that VZV inoculation of the rat results in a single round, incomplete infection that is sufficient to induce pain behaviors, and this involves infection of and changes induced in neuronal populations.
authors.affiliation: Molecular Virology and Microbiology Graduate Program, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, United States; Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, United States.
authors.forename: Jean-Marc G
authors.initials: JM
authors.lastname: Guedon
authors.affiliation: Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, United States.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Yee
authors.affiliation: Department of Microbiology and Molecular Genetics, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, United States.
authors.forename: Mingdi
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, United States.
authors.forename: Stephen A K
authors.initials: SA
authors.lastname: Harvey
authors.affiliation: Department of Microbiology and Molecular Genetics, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, United States.
authors.forename: William F
authors.initials: WF
authors.lastname: Goins
authors.affiliation: Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, United States; Department of Microbiology and Molecular Genetics, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, United States. Electronic address: kinchingtonp@upmc.edu.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Kinchington
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000473:pathology / Q000821:virology; D020869:Gene Expression Profiling; D014645:Herpesvirus 3, Human / Q000502:physiology*; D008297:Male; D046228:Microarray Analysis; D008969:Molecular Sequence Data; D051474:Neuralgia, Postherpetic / Q000473:pathology* / Q000821:virology; D009474:Neurons / Q000473:pathology* / Q000821:virology; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
keywords: Effects of viral infection the nervous system; Pain models; Postherpetic neuralgia; Reporter viruses; Varicella Zoster Virus; Viral induced neuropathy; Viral induced transcriptional changes; Viral post-entry block