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Prevalence and abundance of latently transcribed varicella-zoster virus genes in human ganglia.

ABSTRACT: In human ganglia latently infected with varicella-zoster virus (VZV), sequence analysis has revealed that five viral genes (VZV genes 21, 29, 62, 63, and 66) are transcribed. However, their comparative prevalence and abundance are unknown. Here, using real-time PCR, we analyzed 28 trigeminal ganglia from 14 humans for RNA corresponding to the five virus genes known to be transcribed in latently infected human ganglia. The most prevalent transcript found was VZV gene 63 (78%), followed by gene 66 (43%), gene 62 (36%), and gene 29 (21%). No gene 21 transcripts were detected in any of the 28 ganglia. VZV gene 63 RNA was also the most abundant (3,710 +/- 6,895 copies per 1 microg of mRNA) transcript detected in latently infected human ganglia, followed by VZV gene 29 (491 +/- 594), VZV gene 66 (117 +/- 85), and VZV gene 62 (64 +/- 38). Thus, the repeated detection and high abundance of VZV gene 63 transcripts in latently infected ganglia suggests that VZV gene 63 may be more important for the maintenance of virus latency than the less abundantly transcribed and randomly detected VZV genes 21, 29, 62, and 66.

SUBMITTER: Cohrs RJ

PROVIDER: S-EPMC1866015 | biostudies-literature | 2007 Mar

REPOSITORIES: biostudies-literature

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Prevalence and abundance of latently transcribed varicella-zoster virus genes in human ganglia.

Cohrs Randall J RJ Gilden Donald H DH

Journal of virology 20061227 6

In human ganglia latently infected with varicella-zoster virus (VZV), sequence analysis has revealed that five viral genes (VZV genes 21, 29, 62, 63, and 66) are transcribed. However, their comparative prevalence and abundance are unknown. Here, using real-time PCR, we analyzed 28 trigeminal ganglia from 14 humans for RNA corresponding to the five virus genes known to be transcribed in latently infected human ganglia. The most prevalent transcript found was VZV gene 63 (78%), followed by gene 66 ...[more]

PMID: 17192313

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Project description:Varicella zoster virus (VZV), a human alphaherpesvirus, causes varicella during primary infection. VZV reactivation from neuronal latency may cause herpes zoster, post herpetic neuralgia (PHN) and other neurologic syndromes. To investigate VZV neuropathogenesis, we developed a model using human dorsal root ganglia (DRG) xenografts in immunodeficient (SCID) mice. The SCID DRG model provides an opportunity to examine characteristics of VZV infection that occur in the context of the specialized architecture of DRG, in which nerve cell bodies are ensheathed by satellite glial cells (SGC) which support neuronal homeostasis. We hypothesized that VZV exhibits neuron-subtype specific tropism and that VZV tropism for SGC contributes to VZV-related ganglionopathy. Based on quantitative analyses of viral and cell protein expression in DRG tissue sections, we demonstrated that, whereas DRG neurons had an immature neuronal phenotype prior to implantation, subtype heterogeneity was observed within 20 weeks and SGC retained the capacity to maintain neuronal homeostasis longterm. Profiling VZV protein expression in DRG neurons showed that VZV enters peripherin+ nociceptive and RT97+ mechanoreceptive neurons by both axonal transport and contiguous spread from SGC, but replication in RT97+ neurons is blocked. Restriction occurs even when the SGC surrounding the neuronal cell body were infected and after entry and ORF61 expression, but before IE62 or IE63 protein expression. Notably, although contiguous VZV spread with loss of SGC support would be predicted to affect survival of both nociceptive and mechanoreceptive neurons, RT97+ neurons showed selective loss relative to peripherin+ neurons at later times in DRG infection. Profiling cell factors that were upregulated in VZV-infected DRG indicated that VZV infection induced marked pro-inflammatory responses, as well as proteins of the interferon pathway and neuroprotective responses. These neuropathologic changes observed in sensory ganglia infected with VZV may help to explain the neurologic sequelae often associated with zoster and PHN.

Dataset Information

Prevalence and abundance of latently transcribed varicella-zoster virus genes in human ganglia.

Publications

Prevalence and abundance of latently transcribed varicella-zoster virus genes in human ganglia.

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