| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1994: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
Mouse fibroblast cell lines (L, NIH3T3) supported a low level of measles virus (MV) replication. These fibroblasts never formed multinucleated giant cells, a characteristic cytopathic effect of MV infection. We derived L cell transfectants stably expressing the gene encoding the human CD46, the recently identified MV receptor. Upon infection with MV, these transfectants produced 20 fold more MV, became 100 time more sensitive to MV than the parental L cells, and developed syncytia. To determine the domain (s) in CD46 essential for the receptor function, several deletion mutants were generated that lacked the cytoplasmic region or each one of the four short consensus repeat (SCR) of CD46. Mutants lacking SCR1 or SCR2 were found not to act as the receptor, indicating that SCR1 or SCR2 are indispensable for the function as the MV receptor. On the basis of these results, we produced transgenic mice expressing the human CD46 as an animal model to study immunosuppression observed during MV infection. We are currently testing whether these mice are susceptible to MV, and develop any clinical signs.
We also examined the mechanism by which MV inhibitits thein vitro proliferation of T cells. Coculture with cells expressing MV glycoproteins without producing infectious MV did not lead to the inhibition of the mitogen-induced T cell proliferation, indicating that the cell-cell interaction through MV glycoproteins expressed on MV-infected cells and surface molecules on uninfected cells is not sufficient to cause the inhibition of T cell proliferation.
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