2007 Fiscal Year Final Research Report Summary
Host Cellular responses accompanied by Epstein-Barr Virus genome replication.
| Project/Area Number |
18390147
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Virology
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| Research Institution | Aichi Cancer Center Research Institute |
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Principal Investigator |
TSURUMI Tatsuya Aichi Cancer Center Research Institute, Division of Virology, Chief (90172072)
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| Co-Investigator(Kenkyū-buntansha) |
ISOMURA Hiroki Aichi Cancer Center(Research Institute), Division of Virology, Senior Researcher (20294415)
IWAHORI Satoko Aichi Cancer Center(Research Institute), Division of Virology, Research Resident (80416164)
NAKAYAMA Sanae Aichi Cancer Center(Research Institute), Division of Virology, Research Resident (80443456)
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| Project Period (FY) |
2006 – 2007
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| Keywords | EBV / p53 / ATM / DNA damage / ubiquitilation / MDM2 |
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| Research Abstract |
Induction of the Epstein-Barr virus(EBV) lytic program elicits ATM-dependent DNA damage response, resulting in phosphorylation of p53 at Ser15, which, prevents interaction with MDM2. Nevertheless, p53-downstream signaling is blocked. We found here that during the lytic infection p53 was actively degraded in a proteasome-dependent manner even with a reduced level of MDM2. Turnover of p53 was stimulated in the lytic phase compared with that in the latent phase, indicating that EBV regulates p53 level also after induction of the lytic replication. Co-immunoprecipitation analysis revealed that the EBV BZLF1 immediate-early protein interacted with the DNA-binding domain near the N-terminus of p53. It was confirmed that BZLF1 protein elicited proteasome-dependent degradation of p53. and repressed the p53-mediated transactivation in SaOS-2 cells. The degradation of p53 was observed even in the presence of Nutlin-3, an inhibitor of p53-MDM2 interaction, and also in mouse embryo fibroblasts lacking mdm2 gene, indicating that the BZLF1 protein-induced degradation of p53 was independent of MDM2. Furthermore, Nutlin-3 increased the level of p53 in the latent phase of EBV infection but not in the lytic phase. Thus, although p53 level is regulated by MDM2 in the latent phase, it might be mediated by the BZLF1 protein-associated E3 ubiquitin ligase in the lytic phase, providing the insight that EBV regulates the cellular environment advantageous for lytic replication through degradation of p53, leading to inhibition of p53 downstream signaling pathway.
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[Journal Article] A cis element between the TATA Box and the transcription start site of the major immediate-early promoter of human cytomegalovirus determines efficiency of viral replication.2008
Author(s)
Isomura, H., Stinski, MF., Kudoh, A., Nakayama, S., Murata, T., Sato, Y., Iwahori, S. and Tsurumi, T.
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Journal Title
J Virol 82
Pages: 849-858
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Noncanonical TATA Sequence in the UL44 Late Promoter of Human Cytomegalovirus is required for the accumulation of late viral transcripts.2008
Author(s)
Isomura, H., Stinski, MF., Kudoh, A., Murata, T., Nakayama, S., Sato, Y., Iwahori, S. and Tsurumi, T.
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Journal Title
J virol. 82
Pages: 1638-1646
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The late promoter of the human cytomegalovirus viral DNA polymerase processivity factor has an impact on delayed early and late viral gene products but not on viral DNA synthesis.2007
Author(s)
Isomura, H., Stinski, MF., Kudoh, A., Nakayama, S., Iwahori, S., Sato, Y. and Tsurumi, T.
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Journal Title
J Virol 81
Pages: 6241-6247
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Enhanced phosphorylation of transcription factor Sp1 dependent on Ataxia Telangiectasia-Mutated(ATM) in response to herpes simplex Vvrus Type I infection.2007
Author(s)
Iwahori, S., Shirata, N., Kawaguchi, Y., Weller, SK., Sato., Y., Kudoh, A., Nakayama, S., Isomura, H. and Tsurumi T.
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Journal Title
J Virol 81
Pages: 9653-9664
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Oncolytic virotherapy with an HSV amplicon vector expressing granulocyte-macrophage colony stimulating factor using the replication-competent HSV type 1 mutant HF10 as a helper virus.2007
Author(s)
Kohno, SI., Luo, C., Nawa, A., Fujimoto, Y., Watanabe, D., Goshima, F., Tsurumi, T. and Nishiyama, Y.
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Journal Title
Cancer Gene Ther. 14
Pages: 918-926
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Phosphorylation of MCM4 at sites inactivating DNA helicase activity of the MCM4-6-7 complex during epstein-barr virus productive replication.2006
Author(s)
Kudoh, A., Daikoku, T., Ishimi, Y., Kawaguchi, Y., Shirata, N., Iwahori. S., Isomura. H. and Tsurumi, T.
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Journal Title
J. Virol. 80
Pages: 10064-10072
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Establishment of a novel foreign gene delivery system combining an HSV amplicon with an attenuated replication-competent virus, HSV-1 HF10.2006
Author(s)
Zhang, L., Daikoku, T., Ohtake, K., Ohtsuka, J., Nawa, A., Kudoh, A., Iwahori, S., Isomura, H., Nishiyama, Y., and Tsurumi. T.
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Journal Title
J. Virol. Methods. 137
Pages: 177-183
Description
「研究成果報告書概要(欧文)」より
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