Journal article
Varicella-Zoster Virus Infection Induces Autophagy in both Cultured Cells and Human Skin Vesicles
Journal of virology, Vol.83(11), pp.5466-5476
06/2009
DOI: 10.1128/JVI.02670-08
PMCID: PMC2681990
PMID: 19297471
Abstract
When grown in cultured cells, varicella-zoster virus (VZV) forms many aberrant light particles and produces low titers. Various studies have explored the reasons for such a phenotype and have pointed to impaired expression of specific late genes and at lysosomal targeting of egressing virions as possible causes. In the studies presented here, we report that the autophagic degradation pathway was induced at late time points after VZV infection of cultured cells, as documented by immunoblot analysis of the cellular proteins LC3B and p62/SQSTM1, along with electron microscopy analysis, which demonstrated the presence of both early autophagosomes and late autophagic compartments. Autophagy was induced in infected cells even in the presence of phosphonoacetic acid, an inhibitor of viral late gene expression, thus suggesting that accumulation of immediate-early and early viral gene products might be the major stimulus for its induction. We also showed that the autophagic response was not dependent on a specific cell substrate, virus strain, or type of inoculum. Finally, using immunofluorescence imaging, we demonstrated autophagosome-specific staining in human zoster vesicles but not in normal skin. Thus, our results document that this innate immune response pathway is a component of the VZV infectious cycle in both cultured cells and the human skin vesicle, the final site of virion formation in the infected human host.
Details
- Title: Subtitle
- Varicella-Zoster Virus Infection Induces Autophagy in both Cultured Cells and Human Skin Vesicles
- Creators
- Marie-Noëlle Takahashi - Global Vaccines Technology and Engineering-Bioanalytics, Merck Manufacturing DivisionWallen Jackson - University of IowaDonna T Laird - Global Vaccines Technology and Engineering-Bioanalytics, Merck Manufacturing DivisionTimothy D Culp - Global Vaccines Technology and Engineering-Bioanalytics, Merck Manufacturing DivisionCharles Grose - University of IowaJohn I Haynes - Global Vaccines Technology and Engineering-Bioanalytics, Merck Manufacturing DivisionLuca Benetti - Global Vaccines Technology and Engineering-Bioanalytics, Merck Manufacturing Division
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.83(11), pp.5466-5476
- DOI
- 10.1128/JVI.02670-08
- PMID
- 19297471
- PMCID
- PMC2681990
- NLM abbreviation
- J Virol
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Publisher
- American Society for Microbiology (ASM)
- Language
- English
- Date published
- 06/2009
- Academic Unit
- Stead Family Department of Pediatrics; Infectious Disease (Pediatrics)
- Record Identifier
- 9984093498902771
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