Mechanisms of Varicella-Zoster Virus Neuropathogenesis in Human Dorsal Root Ganglia
- 15 April 2008
- journal article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 82 (8) , 3971-3983
- https://doi.org/10.1128/jvi.02592-07
Abstract
Varicella-zoster virus (VZV) is a human alphaherpesvirus that infects sensory ganglia and reactivates from latency to cause herpes zoster. VZV replication was examined in human dorsal root ganglion (DRG) xenografts in mice with severe combined immunodeficiency using multiscale correlative immunofluorescence and electron microscopy. These experiments showed the presence of VZV genomic DNA, viral proteins, and virion production in both neurons and satellite cells within DRG. Furthermore, the multiscale analysis of VZV-host cell interactions revealed virus-induced cell-cell fusion and polykaryon formation between neurons and satellite cells during VZV replication in DRG in vivo. Satellite cell infection and polykaryon formation in neuron-satellite cell complexes provide mechanisms to amplify VZV entry into neuronal cell bodies, which is necessary for VZV transfer to skin in the affected dermatome during herpes zoster. These mechanisms of VZV neuropathogenesis help to account for the often severe neurologic consequences of herpes zoster.Keywords
This publication has 36 references indexed in Scilit:
- Aberrant infection and persistence of varicella-zoster virus in human dorsal root ganglia in vivo in the absence of glycoprotein IProceedings of the National Academy of Sciences, 2007
- Productive Varicella-Zoster Virus Infection of Cultured Intact Human GangliaJournal of Virology, 2007
- Prevalence and Abundance of Latently Transcribed Varicella-Zoster Virus Genes in Human GangliaJournal of Virology, 2007
- Selective retention of herpes simplex virus-specific T cells in latently infected human trigeminal gangliaProceedings of the National Academy of Sciences, 2007
- Essential Functions of the Unique N-Terminal Region of the Varicella-Zoster Virus Glycoprotein E Ectodomain in Viral Replication and in the Pathogenesis of Skin InfectionJournal of Virology, 2006
- Herpes Simplex Virus gE/gI Must Accumulate in the trans -Golgi Network at Early Times and Then Redistribute to Cell Junctions To Promote Cell-Cell SpreadJournal of Virology, 2006
- Varicella-Zoster Virus ORF63 Inhibits Apoptosis of Primary Human NeuronsJournal of Virology, 2006
- Laser-Capture Microdissection: Refining Estimates of the Quantity and Distribution of Latent Herpes Simplex Virus 1 and Varicella-Zoster Virus DNA in Human Trigeminal Ganglia at the Single-Cell LevelJournal of Virology, 2005
- The Extracellular Domain of Herpes Simplex Virus gE Is Indispensable for Efficient Cell-to-Cell Spread: Evidence for gE/gI ReceptorsJournal of Virology, 2005
- ER-to-Golgi Carriers Arise through Direct En Bloc Protrusion and Multistage Maturation of Specialized ER Exit DomainsDevelopmental Cell, 2003