| Project/Area Number |
16590395
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | National Institute of Infectious Diseases |
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Principal Investigator |
HARADA Shizuko National Institute of Infectious Diseases, ウイルス第一部, 主任研究官 (10218646)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | EBV / virus / latent infection / nuclear protein / transactivation / EBNA |
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| Research Abstract |
Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus that latently infects B-lymphocytes and causes their continuous proliferation into lymphoblastoid cell lines (LCL). EBV nuclear protein EBNA-2 and EBNA-LP are the first viral proteins expressed in lymphocytes. They cooperatively up-regulate EBV and cellular gene transcription, and are required for lymphocyte outgrowth into LCL. Previously, we discovered that mutant EBNALP that contains a 10-amino acid-truncation at its C-terminus does not have the ability to coactivate and it preferentially interacts with the EBNA2 acidic transactivating domain. Furthermore, the mutant EBNALP has a dominant negative effect on the coactivation activity of the wild-type EBNALP. The functional relevance of EBNALP in maintaining LCL cell growth is yet to be characterized. Therefore, we established cell clones derived from an LCL in which a dominant negative form of EBNALP (DNLP) is conditionally expressed by the Cre-loxP system. This was required in order to analyze the effect of DNLP expression on EB V induced cell proliferation. After drug addition, the generated LCL clones expressing DNLP showed retardation of cell proliferation and reduced cell viability. The results indicate that EBNALP plays a critical role in maintaining LCL growth and EB V induced cell proliferation.
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