| Budget Amount *help |
¥11,000,000 (Direct Cost: ¥11,000,000)
Fiscal Year 2000: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1999: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1998: ¥5,700,000 (Direct Cost: ¥5,700,000)
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| Research Abstract |
Several years ago CD46 was identified as a cellular receptor for the Edmonston strain of measles virus, but most clinical isolates of measles virus, which are most efficiently isolated in marmoset B cell line B95a, cannot grow in many CD46^+ cell lines. Although some researchers attributed it to post-entry block in viral replication, others believed that there is a receptor other than CD46 for wild-type measles viruses. In this study, we showed that human SLAM (signaling lymphocytic activation molecule ; also known as CDw150), a recently discovered membrane glycoprotein involved in lymphocyte activation, is a cellular receptor for measles virus, including the Edmonston strain. Transfection with a human SLAM cDNA enabled nonsusceptible cell lines to bind measles virus, support measles virus replication, and develop cytopathic effects. The distribution of SLAM was consistent with the susceptibility of various cell lines to wild-type measles virus strains and with pathology of measles virus infection in humans and monkeys. By examining receptor function of various chimeric SLAM molecules, we also showed that the V domain of human SLAM is necessary and sufficient to interact with the measles virus H protein and allow measles virus entry. The identification of SLAM as a receptor for measles virus opens the way to a better understanding of pathogenesis of measles virus infection, especially measles virus-induced immunosuppression.
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