|Budget Amount *help
¥13,100,000 (Direct Cost : ¥13,100,000)
Fiscal Year 2000 : ¥3,800,000 (Direct Cost : ¥3,800,000)
Fiscal Year 1999 : ¥4,300,000 (Direct Cost : ¥4,300,000)
Fiscal Year 1998 : ¥5,000,000 (Direct Cost : ¥5,000,000)
Following findings were obtained during the two project years.
1)Not only host antibody pressure, but also host cell receptor sialo sugar chains cause a selective pressure for the appearance of host cell variants with alterted receptor binding specificities which may have the ability to transmit from animals to humans.
2)This host range selection is processed by host cell receptor level, because the change of the receptor binding specificity (Neu5Ac2-6Gal→Neu5Ac2-3Gal) appeares as the substitution of the amino acid (Leu226→Gln) located in the receptor binding pocket of the viral hemagglutinin, and the other change of the receptor binding specificity (alteration of the recognition to the molecular species of sialic acid, Neu5Ac2-3Gal→Neu5Gc2-3Gal) also occurres by the single amino acid substitution (Ser228→Gly) located in the potential receptor binding pocket.
3) Epitherial cells in pig trachea has receptor sialosugar chains that binds both of bird and human influenza A viruses (Neu5Ac2-6G
al for humans and Neu5Ac2-3Gal for birds). These results indicate that pig may play as a mixing vessel of human and bird influenza viruses in nature. The host range selection of the receptor binding specificity of the A virus hemagglutinin occurrs during the maintenance of the virus in different host cells which express different receptor sialo-sugar chains.
5) It was found that some non-sialyl sugar chains are effective to bind to influenza viruses isolated from human, avian, and swine hosts. These results indicate that these glycolipids have a function as the second common receptor molecule for human and animal influenza viruses.
6) The above new results show that the molecular mechanism of the transmission of the influenza viruses among the animals is deeply related to the recognition to the receptor sialosugar chains (sialyl linkage, 2-3, 2-6 ; and molecular species of sialic acid, Neu5Ac, Neu5Gc). Therefore, the aim of this project, the elucidation of the mechanism of host range variation and emerging of the new subtype of the hemagglutinin and neuraminidase of influenza viruses is satisfactory progressed. Less