| Project/Area Number |
15580279
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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 |
Applied veterinary science
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| Research Institution | Rakuno (kuen University |
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Principal Investigator |
HAGIWARA Katsuro Rakuno Gakuon University, Veterinary Medicine, Associate Professor, 獣医学部, 助教授 (50295896)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIHARA Chiaki Rakuno Gakuen University, Veterinary Medicine, Professor, 獣医学部, 教授 (90082172)
TANIYANMA Hiroyuki Rakuno Gakuen University, Veterinary Medicine, Professor, 獣医学部, 教授 (90133800)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | BDV / PML / aponptosis / Caspase 3 / Bax / 持続感染 / PML蛋白質 / IFN |
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| Research Abstract |
The interferon (IFN)-induced proznyelocytic leukemia (PML) protein is associated with nuclear bodies (NBs) whose functions remain poorly understood. Overexpression of PML has been shown to affect the replication of several RNA viruses, including influenza and the complex retrovirus human foamy virus (HFV). Various viruses induce disorganization of the PML NBs, which is thought to be part of a general viral strategy to counteract IFN action. The mononegavirus Boron disease virus (BDV) can persistently infect neurons and astrocytes in the rat central nervous system (CNS) in the presence of a robust IFN response. Replication and transcription of BDV occur in the nucleus, a unique feature among known animal mononegaviruses. BDV antigens colocalize with PML, and persistence of BDV induces PML NBs disorganization suggesting a possible mechanism whereby BDV counteract the IFN response. Vero cells do not produce IFN, hence facilitating the evaluation of PML antiviral activity in the absence of
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other IFNinduced genes. Overexpression of PML via a recombinant adenovirus (AdPML) induced high levels of PML NBs structures in Vero cells, but did not exert any antiviiral activity against BDV Virus titers, as well as levels of BDV replication and transcription were similar in Vero cells that were infected with AdPML or mock-infected prior infection with BDV. In contrast, and consistent with a previous report, infection with AdPML resulted in about 1000-fold decrease in the production of infectious VSV. NBs have been implicated in hormone signaling, and glucocorticoids are potent modulators of astrocyte function. The resistance of BDV to the antiviral action of PML together with BDV mediated disorganization of PML NBs may contribute to disturbances in CNS function associated with BDV persistence.
PML is required for p53 pro-apoptotic signaling, as well as growth arrest inducing pathways. BDV persistence provides increased resistance to program cell death following exposure to Camptothecin. This effect was associated with impaired expression of the pro-apoptotic genes Caspase 3 and Bax. Protection from apoptosis was also observed in cells transfected with BDV N, Together these findings suggest that BDV N might be a repressor of apoptosis, an activity that could contribute to the exquisite ability of BDV to persist in brain cells. Less
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