Grant-in-Aid for International Scientific Research.
|Section||Joint Research .|
|Research Institution||UNIVERSITY OF SHIZUOKA|
SUZUKI Yasuo UNIVERSITY OF SHIZUOKA,SCHOOL OF PHARMACEUTICAL SCIENCES,PROFESSOR, 薬学部, 教授 (00046278)
ITZSTEIN Mar Monash University Victorian college of P, 教授
THAWATSUPHA Virus Res. Inst., Ministry of Public Healt, 主幹
SHORTRIDGE K University of Hong Kong, 教授
河岡 義裕 ウイスコンシン大学, 獣医学部, 教授
WEBSTER Robe St. Jude Children's. Res. Hospital Dept. Vir, 部長
ショートリッジ ケネディ ホンコン大学, 教授
フォン・イツスタイン マ モナーシュ大学, ビクトリア校・薬学部, 教授
プラニー タワ タイ公衆衛生局ウイルス研究部, 主幹
ウェブスター ロバート・ 聖ユダ小児研究病院, ウイルス・分子生物学部, 部長
SHORTRIDGE Kenney F. UNIVERSITY OF HONG KONG
THAWATSUPHA Pranee VIRUS RES.INST.MINISTRY PUBLIC HEALTH,THAILAND,CHIEF
WEBSTER Robert G. ST.JUDE CHILDREN'S RES.HOSPITAL,DEPT.VIROL.MOL.BIOL., CHAIRMAN
KAWAOKA Yoshihiro UNIVERSITY OF WISCONSIN,SCHOOL OF VET.MED.PROFESSOR
ITZSTEIN Mark von MONASH UNIVERSITY,VICTORIAN COLLEGE OF PHARM.PROFESSOR
|Project Fiscal Year
1997 – 1998
Completed(Fiscal Year 1998)
|Budget Amount *help
¥8,800,000 (Direct Cost : ¥8,800,000)
Fiscal Year 1998 : ¥4,200,000 (Direct Cost : ¥4,200,000)
Fiscal Year 1997 : ¥4,600,000 (Direct Cost : ¥4,600,000)
|Keywords||INFLUENZA VIRUS / INFLUENZA / ASIA / SIALIC ACID / SUGAR CHAIN / HEMAGGLUTININ / NUERAMINIDASE / HOST RANGE VARIATION / インフルエンザウイルス / インフルエンザ / アジア / シアル酸 / 糖鎖 / ヘマグルチニン / ノイラミニダーゼ / 宿主域変異 / 変異 / 受容体|
1) We propose here that 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) Epitherial cells in pig trachea has receptor sialosugar chains that binds both of bird and human influenza A viruses (Neu5Ac2-6Gal 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.
3) This host range selection is processed by host cell receptor level, and also by antibody pressure, brcause the change of the receptor binding specificity (Neu5Ac2-6Gal* Neu5Ac2-3Gal) appeares as the substitution of the amino acid (Leu226*GIn) located in the receptor bi
nding pocket of the viral hemagglutinin, and the other change of the receptor binding specificity (Neu5Ac2-3Gal*Neu5Ac2-6Gal) also occurres by the single amino acid substitution (Ser2O5*Tyr) located in the potential anigenic site D outside from the pocket.
4) The variation of the viral hemagglutinin molecule among the host animals and cells also caused the change of their recognition of the 2 major molecular species of terminal sialic acid (Neu5Ac, Neu5Gc) in nature. The influenza viruses isolated from pigs and horses can bind to Neu5Gc (a major sialic acid molecular species of pigs and horses) -containing sugar chains, as well as Neu5Ac-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.
The above new results show that the aim of this project is satisfactory progressed, and the fundamental experimantal results to elucidate the mechanism of host range variation and emerging of the new subtype of the hemagglutinin and neuraminidase of influenza viruses in Asia and to establish the fundamental idea for the control of the influenza virus variation. Less