Neuronal Subtype and Satellite Cell Tropism Are Determinants of Varicella-Zoster Virus Virulence in Human Dorsal Root Ganglia Xenografts In Vivo

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