Regulation Mechanisms of HIV LTR Demethylation through Reactivation Signaling
| Project/Area Number |
12670274
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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 | The University of Tokyo |
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Principal Investigator |
ISHIDA Takaomi The University of Tokyo, The Institute of Medical Science, Research Associate, 医科学研究所, 助手 (80293447)
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| Co-Investigator(Kenkyū-buntansha) |
IWAKURA Yoichiro The University of Tokyo, The Institute of Medical Science, Proffesor, 医科学研究所, 教授 (10089120)
WATANABE Toshiki The University of Tokyo, The Institute of Medical Science, Associate Proffesor, 医科学研究所, 助教授 (30182934)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | HIV / LTR / Transcription / CpG Methylation / Latent Infection / LTR / 転写抑制 / 潜伏感染 / Histone Code / クロマチン免疫沈降法 / ヌクレオソーム / 潜伏HIV再活性化シグナルによるLTRの脱メチル化制御 / 細胞内シグナル伝達 |
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| Research Abstract |
Introduction of potent anti-HIV combination chemotherapy has focused reseacher's interest on the mechanisms of viral latency, because eradication of HIV cannot be achieved without eradication of latent HIV in reservoir pool. CpG methylation has long been impricated in the viral latency as one base for repression of gene expression. We could find that the levels of CpG methylation were inversly correlated with the viral gene expression in chironically infected cell lines. Induction of viral gene expresson by TNF-α in ACH-2 cell line was shown to be associated with demethylation of CpG sequence in the provirus LTR.
Because we could find that 5'-LTR specific methylation was occurred in the HTLV-1 provirus LTR, we designed the bisulfite modified PCR sense primer located in the 5'-flanking sequence of the integrated provirus and that in the tat coding region and selectively methylation status analyzed. Results revealed selective hypermethylation of 5'-LTR and hypomethylation of 3'-LTR in the ACH-2 cell line. The same selectivity was observed in the chilonically infected cell lines, ATL cases and HTLV-1 asymptomatic carriers. It was possible that mammalian cells has the ability to hypermethylate the integrated retrovirus 5'-LTR or to demethylate the 3'-LTR.
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Report
(3 results)
Research Products
(6 results)
