Analysis of molecular bases determining tropism of negative strand viruses
| Project/Area Number |
15590411
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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 | University of Tsukuba |
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Principal Investigator |
TAKEUCHI Kaoru University of Tsukuba, Graduate School of Comprehensive Human Sciences, Associated Professor, 大学院・人間総合科学研究科, 助教授 (00192162)
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| Co-Investigator(Kenkyū-buntansha) |
NAGATA Kyosuke University of Tsukuba, Graduate School of Comprehensive Human Sciences, Professor, 大学院・人間総合科学研究科, 教授 (40180492)
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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 |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | measles virus / reverse genetics / tropism / envelope protein / receptor / accessory protein / インターフェロン / 感染防御 / シグナル伝達 / 蛋白質リン酸化 |
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| Research Abstract |
The P gene of measles virus (MV) encodes the P protein and three accessory proteins (C,V and R). However, the role of these accessory proteins in the natural course of MV infection remains unclear. Here, we generated a recombinant wild-type MV lacking the C protein, wtMV(C-), using a reverse genetics system (Takeda et al., J.Virol.74:6643-6647). When 293 cells expressing the MV receptor SLAM (293/hSLAM) were infected with wtMV(C-) or parental wtMV, growth of wtMV(C-) was restricted, particularly in late stages. Consistently, EGFP-expressing wtMV(C-) induced late-stage cell rounding and cell death in the presence of the fusion-inhibiting peptide, suggesting that the C protein can prevent cell death and is required for long-term MV infection. Neutralizing antibodies against interferon-α/β did not restore the growth restriction of wtMV(C-) in the 293/hSLAM cells. When cynomolgus monkeys were infected with wtMV(C-) or wtMV, the number of MV-infected cells in the thymus was more than 1,000-fold lower for wtMV(C-) than wtMV. Immunohistochemical analyses showed strong expression of a MV antigen in the spleen, lymph nodes, tonsils and larynx of cynomolgus monkey infected with wtMV, but dramatically reduced expression in those tissues in cynomolgus monkey infected with wtMV(C-). These data indicate that the MV C protein is necessary for efficient MV replication both in vitro and in cynomolgus monkeys.
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Report
(3 results)
Research Products
(18 results)
