| Project/Area Number |
14570274
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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 Disease |
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Principal Investigator |
HARADA Shizuko National Institute of Infectious Disease, ウイルス第一部, 主任研究官 (10218646)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | EBV / virus / latent infection / nuclear protein / transactivation / EBNA / ドミナントネガティブ |
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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. We have now found that EBNA-LP readily associated with EBNA2 or with the EBNA2 C-terminal activation domain (E2AD) when both components were expressed in bacteria. In lymphoblasts, EBNA-LP and EBNA2 did not stably associate. However, EBNA-LP deleted for only 10 C-terminal amino acids (aa) stably associated with EBNA2 in lympohoblasts. EBNA-LP 31 aa (dW2Y1) with 24 C-or N-terminal aa was a specific and efficient affinity matrix for EBNA2 or EBNA-LP. These biochemical interactions between EBNA-LP and EBNA2 enable coordinated transcriptional regulation of cell and viral gene expression in lymphoblasts only when the interaction is unstable ; deletion of the EBNA-LP C-terminal 10aa stabilizes association with EBNA2 and prevents co-activation. Since EBNA-LPd10 dominantly inhibited EBNA-LP co-activation with EBNA2, EBNA-LP d10 over-expression in LCLs may be useful in assessing the role of EBNA-LP co-activation in LCL growth or survival.
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