| Project/Area Number |
09670316
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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 | Osaka University |
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Principal Investigator |
KONDO Kazuhiro Osaka University Medical School, Associate Professor, 医学部, 助教授 (70234929)
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| Co-Investigator(Kenkyū-buntansha) |
TAYA Keiko Osaka University Medical School, Assistant Professor, 医学部, 助手 (80263276)
INAGI Reiko Osaka University Medical School, Assistant Professor, 医学部, 助手 (50232509)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1997: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | human herpesvirus 6 / latency / reactivation / cytomegalovirus / human herpesvirus 7 / マクロファージ / 神経膠細胞 |
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| Research Abstract |
Human cytomegalovirus (CMV) is a significant pathogen in immunocompromised individuals and neonates. Human herpesvirus 6 (HHV-6) is a causative agent of exanthem subitum. These two virusues belong to b-herpesvirus subfamily. Latency, a hallmark of all herpesvirus, remains poorly understood for b-herpesvirus. We investigate maintenance and expression of the viral genome in an experimental latent infection using granulocyte-macrophage progenitors (GM-Ps) for CMV and monocytes/macrophages for HHV-6. Following infection with cytomegalovirus, human GM-Ps carry the viral genome but fail to support productive replication. HHV-6 maintein its genome in human monocytes/macrophages.
To better understand b-herpesvirus latency, we investigate the extent of viral gene expression in our latency system and found two novel classes of CMV latency associated transcripts (CLTs) and HHV-6 latency transcript (HHV-6LT). We characterize these transcripts and CLTs can be detected in BM aspirates from healthy CMV seropositive adults and HHV-6LT from healthy individuals. Both in the case of CMV and HHV-6, viral transcripts arise from a region encompassing the major regulatory gene locus ; however, their structure differs significantly from productive phase transcripts. In the case of CMV, these transcripts have the potential to encode novel 94 and 152aa proteins. In HHV-6 novel 99aa, 279aa, 91aa and 160aa proteins are encorded. Thus, latent infection by CMV and HHV-6 is accompanied by the presence of latency-associated transcripts and expression of immunogenic proteins. Overall, these results suggest that bone marrow-derived myeloid progenitors are an important natural site of CMV latency and peripheral blood derived monocytes/macrophages is important to maintein HHV-6 latency.
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