| Research Abstract |
This project is aimed to reveal the mechanism relationships between the evolution of the influenza viruses and the recognition of the receptor sialo-sugar chains in the host cells. Several findings obtained during the term of the project are as follows: 1, Receptor sialo-sugar chains including the molecular species of sialic acids and the sialo-sugar chain sequences for human and animal (birds, equine, porcine) influenza A, B, and C viruses were firstly identified. Several hydridomas that produces monoclonal antibody directed to the receptor sugar chains were also established. 2, Hemagglutinin genes of all subtypes (H1-H13) of the influenza A viruses and their receptor specificity were identified. All hemagglutinin subtypes recognized common receptor sugar chains, such as lacto-series type I and II chains, and the variation of the hemagglutinin genes showed the change of the recognition only to sialyl-Gal linkage (2-3, 2-6). 3, New inhibitors of the neuraminidase (thio-glycoside gangli
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o-sides), a receptor destroying enzyme, were found and the three dimensional interactions between the inhibitors (ganglioside-analogs) and the neuraminidase was studied by X-ray diffraction study. This project was performed with Dr. Peter M. Colman (CSIRO), one of the co-investigators of this project. 4, A new glycoproteins which bind to influenza virus hemagglutinin, but are resistant to viral neuraminidase were found in several animal sera. These have strong neutralizing activity of infuenza viruses, indicating that these glycoproteins are possible candidates as a native inhibitor or drug of the influenza viruses. This work was performed with Dr.Robert G.Webster (St.Jude children's Res.Hospital), other co-investigator of this project. 5, The strategy for the development of a new anti-influenza drug and a universal vaccine which generates the antibody whose supervariable region mimics the common receptor sialo-sugar chains for all the subtypes of influenza viruses is also studied, and some hybridoma clones which produce anti-receptor sialo-sugar chains idiotype antibody were established. These anti-idiotype antibodies inhibit the binding between the receptor and the many kinds of influenza virus variants. Less
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