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Purification of Viral DNA for the Identification of Associated Viral and Cellular Proteins
Published on: August 31, 2017
Human Herpesvirus-6 U14 Induces Cell-Cycle Arrest in G2/M Phase by Associating with a Cellular Protein, EDD
Junko Mori1, Akiko Kawabata1, Huamin Tang2
1Division of Clinical Virology, Kobe University Graduate School of Medicine, Kobe, 6500017, Japan.
Abstract:
The human herpesvirus-6 (HHV-6) infection induces cell-cycle arrest. In this study, we found that the HHV-6-encoded U14 protein induced cell-cycle arrest at G2/M phase via an association with the cellular protein EDD, a mediator of DNA-damage signal transduction. In the early phase of HHV-6 infection, U14 colocalized with EDD dots in the nucleus, and similar colocalization was also observed in cells transfected with a U14 expression vector. When the carboxyl-terminal region of U14 was deleted, no association of U14 and EDD was observed, and the percentage of cells in G2/M decreased relative to that in cells expressing wild-type U14, indicating that the C-terminal region of U14 and the U14-EDD association are critical for the cell-cycle arrest induced by U14. These results indicate that U14 is a G2/M checkpoint regulator encoded by HHV-6.
Insights
Human herpesvirus-6 (HHV-6) infection causes cell-cycle arrest. The HHV-6 U14 protein interacts with cellular EDD protein, leading to G2/M phase arrest, crucial for viral replication.
Area of Science:
- Virology
- Cell Biology
- Molecular Biology
Background:
- Human herpesvirus-6 (HHV-6) is known to induce cell-cycle arrest.
- Understanding the molecular mechanisms behind HHV-6-induced cell-cycle regulation is crucial for comprehending viral pathogenesis.
Purpose of the Study:
- To investigate the role of the HHV-6-encoded U14 protein in inducing cell-cycle arrest.
- To elucidate the interaction between HHV-6 U14 protein and cellular factors involved in cell-cycle regulation.
Main Methods:
- Cell-cycle analysis of HHV-6 infected cells.
- Co-immunoprecipitation assays to detect protein-protein interactions.
- Analysis of U14 protein mutants to identify critical domains for EDD interaction and cell-cycle arrest.
Main Results:
- The HHV-6 U14 protein induces cell-cycle arrest at the G2/M phase.
- U14 protein associates with the cellular DNA-damage mediator EDD.
- The C-terminal region of U14 is essential for its association with EDD and subsequent G2/M phase arrest.
Conclusions:
- HHV-6 U14 protein acts as a G2/M checkpoint regulator.
- The interaction between U14 and EDD is critical for HHV-6-mediated cell-cycle arrest.
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