MOLECULAR MECHANISM OF HOST MEDIATED VARIATION OF INFLUENZA VIRUSES AND ITS CONTROL

在两个项目中得到了以下发现：1)不仅宿主抗体压力，而且宿主细胞受体唾液酸糖链对具有从动物到人类传播能力的受体结合特异性改变的宿主细胞变异体的出现造成选择压力。2)这种宿主范围的选择是由宿主细胞受体水平进行的，因为受体结合特异性的变化(Neu5Ac2-6Gal→Neu5Ac2-3Gal)表现为位于病毒血凝素受体结合口袋中的氨基酸(Leu226→Gln)的替代，以及受体结合特异性的其他变化(对唾液酸分子种类的识别改变，Neu5Ac2-3GalNeu5Ac2-3Gal→(Neu5Ac2-3GalNeu5Ac2-3Gal)也是通过潜在受体结合口袋中的单一氨基酸(Ser228→Gly)发生的。3)猪气管上皮细胞具有与禽流感病毒和人类流感病毒(Neu5Ac2-6G…)结合的受体唾液糖链更多的Al用于人类，Neu5Ac2-3Gal用于鸟类)。这些结果表明，猪在自然界中可能是人和禽流感病毒的混合容器。甲型流感病毒血凝素受体结合特异性的宿主范围选择发生在病毒在不同宿主细胞中维持的过程中，这些宿主细胞表达不同的唾液酸糖链。5)研究发现，一些非唾液酸糖链可以有效地与人、禽和猪分离的流感病毒结合。以上新结果表明，流感病毒在动物间传播的分子机制与对受体唾液酸链(唾液酸链，2-3，2-6；唾液酸，Neu5Ac，Neu5Gc)的识别密切相关。因此，本项目的目标是阐明流感病毒血凝素和神经氨酸酶新亚型的宿主范围变异和产生的机制，取得了令人满意的进展。较少

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 … More 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