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11:28
Dissecting Host-virus Interaction in Lytic Replication of a Model Herpesvirus
Published on: October 7, 2011
The neuronal host cell factor-binding protein Zhangfei inhibits herpes simplex virus replication
Oksana Akhova1, Matthew Bainbridge, Vikram Misra
1Department of Veterinary Microbiology, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, Saskatchewan S7N 5B4, Canada.
Journal of Virology
|November 12, 2005
Summary
Zhangfei, a neuron-specific protein, inhibits herpes simplex virus type 1 (HSV-1) immediate-early gene expression by blocking the VP16-HCF-Oct-1 complex formation, aiding viral latency.
Area of Science:
- Virology
- Neuroscience
- Molecular Biology
Background:
- Herpes simplex virus type 1 (HSV-1) lytic infection relies on the VP16-HCF-Oct-1 complex for immediate-early (IE) gene expression.
- HSV-1 establishes latency in sensory neurons, requiring suppression of viral gene activation.
- The cellular protein Zhangfei binds HCF and inhibits another HCF-binding transcription factor, Luman/LZIP/CREB3.
Purpose of the Study:
- To investigate the role of Zhangfei in HSV-1 gene expression and viral latency.
- To determine if Zhangfei selectively inhibits HSV-1 immediate-early gene activation.
Main Methods:
- Assessed Zhangfei expression in human neurons.
- Delivered Zhangfei to cultured cells to observe its effect on VP16-mediated HSV-1 IE expression.
- Utilized Gal4-VP16 chimeric protein assays to confirm specificity.
- Analyzed Zhangfei's interaction with VP16 and its effect on complex formation.
- Measured HSV-1-induced cellular gene expression.
Main Results:
- Zhangfei is selectively expressed in human neurons.
- Exogenous Zhangfei inhibited VP16's activation of HSV-1 IE gene expression.
- Inhibition was specific to HCF-dependent activation on TAATGARAT promoters.
- Zhangfei directly associated with VP16, preventing VP16-HCF-Oct-1 complex assembly.
- Zhangfei suppressed HSV-1-induced expression of cellular genes like topoisomerase IIalpha.
Conclusions:
- Zhangfei acts as a neuronal repressor of HSV-1 immediate-early gene expression.
- Zhangfei's mechanism involves direct interaction with VP16, disrupting crucial transcription factor complex formation.
- Zhangfei may play a role in suppressing HSV-1 DNA replication and late gene expression, contributing to viral latency.
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