Pocket protein p130/Rb2 is required for efficient herpes simplex virus type 1 gene expression and viral replication
G L Ehmann1, H A Burnett, S L Bachenheimer
1Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, North Carolina 27599-7290, USA.
Journal of Virology
|July 4, 2001
Summary
Herpes simplex virus type 1 (HSV-1) infection halts cell cycle progression. The pocket protein p130 is crucial for HSV-1 to inhibit cyclin-dependent kinase 2 (CDK2) activity and promote viral DNA replication.
Area of Science:
- Virology
- Cell Biology
- Molecular Biology
Background:
- Herpes simplex virus type 1 (HSV-1) infection disrupts mammalian cell cycle progression, leading to a G1-like state.
- This disruption is characterized by decreased cyclin-dependent kinase 2 (CDK2) activity, loss of hyperphosphorylated retinoblastoma protein (pRb), and impaired DNA replication.
Purpose of the Study:
- To investigate the roles of pocket proteins pRb, p107, and p130 in HSV-1-induced cell cycle inhibition.
- To understand their involvement in regulating cyclin kinase activity during viral infection.
Main Methods:
- Infection of murine 3T3 cells derived from wild-type (WT) and knockout embryos (pRb(-/-), p107(-/-), p130(-/-), p130(-/-)/p107(-/-)) with HSV-1.
- Assessment of CDK2 activity, viral protein accumulation, viral DNA replication, and progeny virus yield.
Main Results:
- WT, pRb(-/-), and p107(-/-) cells showed similar responses to HSV-1 infection regarding CDK2 inhibition, viral protein accumulation, and DNA replication.
- p130(-/-) cells exhibited no CDK2 inhibition, delayed viral protein accumulation, impaired viral DNA replication compartments, and reduced viral DNA synthesis, resulting in a 2-log decrease in progeny virus yield.
- p130(-/-)/p107(-/-) double-knockout cells displayed an intermediate viral replication phenotype.
Conclusions:
- The pocket protein p130 plays a critical role in regulating cell cycle progression during HSV-1 infection.
- p130 is essential for the timely expression of viral genes and efficient replication of viral DNA.
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