| Project/Area Number |
11470073
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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 | Hokkaido University |
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Principal Investigator |
TAKADA Kenzo Hokkaido Univ., Institute for Genetic Medicine, Prof., 遺伝子病制御研究所, 教授 (30133721)
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| Co-Investigator(Kenkyū-buntansha) |
MARUO Seiji Hokkaido Univ., Institute for Genetic Medicine, Inst., 遺伝子病制御研究所, 助手 (70292018)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥15,800,000 (Direct Cost: ¥15,800,000)
Fiscal Year 2000: ¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 1999: ¥9,500,000 (Direct Cost: ¥9,500,000)
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| Keywords | Epstein-Barr virus / LMP2A / latent infection / membrane immunoglobulin / 活性化 / カルシウム動員 |
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| Research Abstract |
To quantitatively evaluate the role of Epstein-Barr virus (EBV)-encoded latent membrane protein 2A(LMP2A) in immortalization of peripheral B-lymphocytes, we used the Akata cell system to generate an EBV recombinant in which the first exon of the LMP2A gene was disrupted. The results indicated that deletion of the LMP2A gene did not affect the immortalization efficiency of EBV in B-lymphocytes. Deletion of the LMP2A gene made EBV-transformed lymphocytes more permissive for virus replication in response to surface immunoglobulin cross-linking. On the other hand Akata cells, in which LMP2A expression was much lower than in EBV-transformed lymphocytes, were equally permissive for virus replication whether they were infected with wild EBV or LMP2A-knockout EBV. The results raise a question as to the role of LMP2A in inhibition of disruption of virus latency in vivo, where LMP2A expression has been expected to be low as in Akata cells. Furthermore, to clarify the strain variation of the LMP2A gene, we determined the nucleotide sequence of the LMP2A gene of Akata strain and compared it with that of B95-8 strain. Three nucleotide differences were found between Akata and B95-8 strains, which resulted in three amino acid changes, but the two ITAM motifs that were important for blocking signal transduction through crosslinking of B-cell surface immunoglobulins were conserved in two EBV strains. These results suggest that the LMP2A genes of both viruses are not functionally different.
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