| Project/Area Number |
13226089
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | KYUSHU UNIVERCITY |
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Principal Investigator |
YANAGI Yusuke Kyushu University, Faculty of Medicine, Professor, 大学院医学研究院, 教授 (40182365)
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| Project Period (FY) |
2001 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥64,600,000 (Direct Cost: ¥64,600,000)
Fiscal Year 2005: ¥16,500,000 (Direct Cost: ¥16,500,000)
Fiscal Year 2004: ¥16,500,000 (Direct Cost: ¥16,500,000)
Fiscal Year 2003: ¥17,600,000 (Direct Cost: ¥17,600,000)
Fiscal Year 2002: ¥14,000,000 (Direct Cost: ¥14,000,000)
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| Keywords | measles virus / virus receptor / SLAM / CD150 / animal model / 麻疹ウイルス / インターフェロン / レセプター |
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| Research Abstract |
Measles virus (MV) causes a common acute infectious disease characterized by fever, cough and a generalized maculopapular rash. It mainly targets cells of the immune system, and induces profound immunosuppression. Signaling lymphocyte activation molecule (SLAM ; also called CD150), which is expressed on cells of the immune system, acts as a cellular receptor for MV. In this study, we have revealed the following findings.
1. Few viruses in the bodies of patients with measles use CD46, a receptor for vaccine strains of MV.
2. MV can, albeit inefficiently, infect SLAM-negative cells via a SLAM-and CD46-independent pathway.
3. MV may adapt to use CD46 as an alternative receptor through the changes in the H protein. The changes in M and L proteins may also allow MV to adapt to the efficient growth on cultured cells by facilitating MV replication at post-entry steps.
4. Measles, canine distemper and rinderpest viruses are members of the genus Morbillivirus. Canine distemper and rinderpest viruses use dog and cow SLAM as cellular receptors, respectively.
5. The V domain of the human SLAM is necessary and sufficient for MV receptor function, and a residue at position 61 and its adjacent residues in SLAM play important roles in its interaction with the H protein of MV
6. SLAM knockin mice in which the V domain of mouse SLAM is replaced by the corresponding human molecule reproduce the tropism of MV.
These results indicate that SLAM is the principal cellular receptor for MV in vivo, and that SLAM plays an important role in the tropism and pathogenesis of MV. Furthermore, SLAM knockin mice will prove a useful small animal model in elucidating detailed pathogenesis and immune responses during MV infection.
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