Neuronal Subtype and Satellite Cell Tropism Are Determinants of Varicella-Zoster Virus Virulence in Human Dorsal Root Ganglia Xenografts
Varicella zoster virus (VZV) causes varicella; herpes zoster results from VZV reactivation and is associated with post herpetic neuralgia (PHN). We hypothesized that VZV exhibits neuron-subtype specific tropism and that VZV tropism for satellite glial cells (SGC) results in loss of SGC functions that support neurons and contributes to VZV-related ganglionopathy. Using human DRG xenografts in SCID mice, we demonstrated that initial VZV access to neuronal cell bodies occurs by the axonal route, followed by axonal and contiguous spread between neuron-satellite cell complexes. VZV replication is restricted in mechanoreceptive neurons compared to nociceptive neurons. Despite restricted infection, mechanoreceptive neurons were selectively depleted in association with SGC loss following acute DRG infection. VZV infection of DRG triggers release of pro-inflammatory cytokines that cause neuronal damage. These observations may help to explain the neurologic sequelae often associated with herpes zoster and PHN.
Vyšlo v časopise:
Neuronal Subtype and Satellite Cell Tropism Are Determinants of Varicella-Zoster Virus Virulence in Human Dorsal Root Ganglia Xenografts. PLoS Pathog 11(6): e32767. doi:10.1371/journal.ppat.1004989
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1004989
Souhrn
Varicella zoster virus (VZV) causes varicella; herpes zoster results from VZV reactivation and is associated with post herpetic neuralgia (PHN). We hypothesized that VZV exhibits neuron-subtype specific tropism and that VZV tropism for satellite glial cells (SGC) results in loss of SGC functions that support neurons and contributes to VZV-related ganglionopathy. Using human DRG xenografts in SCID mice, we demonstrated that initial VZV access to neuronal cell bodies occurs by the axonal route, followed by axonal and contiguous spread between neuron-satellite cell complexes. VZV replication is restricted in mechanoreceptive neurons compared to nociceptive neurons. Despite restricted infection, mechanoreceptive neurons were selectively depleted in association with SGC loss following acute DRG infection. VZV infection of DRG triggers release of pro-inflammatory cytokines that cause neuronal damage. These observations may help to explain the neurologic sequelae often associated with herpes zoster and PHN.
Zdroje
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