Abstract |
The ability of herpes simplex virus 1 (HSV-1) to replicate efficiently in differentiated cells is regulated by cellular factors that stimulate viral gene expression, cell survival, and viral morphogenesis. Activation of the canonical Wnt signaling pathway generally increases β- catenin protein levels, cell survival, and growth in dividing cells suggesting this important signaling pathway regulates productive infection. In this study, we demonstrated that a β- catenin specific small molecule inhibitor ( iCRT14) reduced HSV-1 titers approximately 10-fold in primary human lung fibroblasts and Vero cells. Furthermore, β- catenin dependent transcription was increased at late times after infection and as expected iCRT14 reduced β- catenin dependent transcription. Although HSV-1 infection increased β- catenin steady state protein levels approximately 4-fold in Vero cells, there was only a nominal increase in human lung fibroblasts. We hypothesized that VP16 regulates β- catenin dependent transcription because VP16 is a viral regulatory protein expressed at late times after infection. In the absence of other viral proteins, VP16 increased β- catenin dependent transcription and β- catenin steady state protein levels. Collectively, these studies suggested the cellular transcription factor β- catenin stimulates productive infection, in part because VP16 enhances β- catenin dependent transcription.
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Authors | Liqian Zhu, Clinton Jones |
Journal | Virus research
(Virus Res)
Vol. 256
Pg. 29-37
(09 02 2018)
ISSN: 1872-7492 [Electronic] Netherlands |
PMID | 30077727
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Copyright | Copyright © 2018 Elsevier B.V. All rights reserved. |
Chemical References |
- Herpes Simplex Virus Protein Vmw65
- beta Catenin
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Topics |
- Animals
- Cells, Cultured
- Epithelial Cells
(virology)
- Fibroblasts
(virology)
- Herpes Simplex Virus Protein Vmw65
(metabolism)
- Herpesvirus 1, Human
(growth & development)
- Host-Pathogen Interactions
- Humans
- Viral Load
- Virus Replication
- Wnt Signaling Pathway
- beta Catenin
(metabolism)
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