Academic Journal
Repression of varicella zoster virus gene expression during quiescent infection in the absence of detectable histone deposition.
| Title: | Repression of varicella zoster virus gene expression during quiescent infection in the absence of detectable histone deposition. |
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| Authors: | Jiayi Wang, Nadine Brückner, Simon Weissmann, Thomas Günther, Shuyong Zhu, Carolin Vogt, Guorong Sun, Rongrong Guo, Renzo Bruno, Birgit Ritter, Lars Steinbrück, Benedikt B Kaufer, Daniel P Depledge, Adam Grundhoff, Abel Viejo-Borbolla |
| Source: | PLoS Pathogens, Vol 21, Iss 2, p e1012367 (2025) |
| Publisher Information: | Public Library of Science (PLoS), 2025. |
| Publication Year: | 2025 |
| Collection: | LCC:Immunologic diseases. Allergy LCC:Biology (General) |
| Subject Terms: | Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5 |
| More Details: | Varicella zoster virus (VZV) is a human-specific herpesvirus that establishes latency in peripheral neurons. The only transcripts detected in infected human trigeminal ganglia (TG) obtained shortly after death correspond to the VZV latency-associated transcript (VLT) and associated VLT-ORF63 splice variants. In vitro studies showed that VLT-ORF63 is translated into a protein (pVLT-ORF63) that induces VZV transcription. The mechanisms that lead to this restricted gene expression and the transition to lytic replication remain unknown, partly due to the difficulty of working with human neurons. In this study, we addressed whether the neuroblastoma-derived cell line SH-SY5Y could serve as a model to investigate the mechanisms that lead to repression of VZV gene expression followed by reactivation. VZV productively infected differentiated SH-SY5Y (dSH-SY5Y) whereas incubation with acyclovir (ACV) inhibited virus replication and induced a progressive repression of the virus. Upon removal of ACV there was production of viral particles in a subset of cells, while others contained non-replicating VZV genomes and VLT-containing transcripts for at least 20 days post-infection (dpi). Exogenous expression of VLT-ORF63 induced productive infection, suggesting that the non-replicating and repressed genomes remained functional. Interestingly, histone deposition was undetectable at VZV genomes in quiescently infected dSH-SY5Y cells, pointing to a potential novel mechanism leading to VZV repression in this neuronal setting. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 1553-7366 1553-7374 |
| Relation: | https://doaj.org/toc/1553-7366; https://doaj.org/toc/1553-7374 |
| DOI: | 10.1371/journal.ppat.1012367 |
| Access URL: | https://doaj.org/article/4ae89ea9e09745b091d9d1082e88e551 |
| Accession Number: | edsdoj.4ae89ea9e09745b091d9d1082e88e551 |
| Database: | Directory of Open Access Journals |
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| ISSN: | 15537366 15537374 |
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| DOI: | 10.1371/journal.ppat.1012367 |
| Published in: | PLoS Pathogens |
| Language: | English |