The objective of the research is to design ways of controlling epidemic influenza in the human population. If the molecular interactions involved in establishing influenza infection and in resisting this infection can be determined, it may be possible to design rational control measures which are derived from knowledge of the nature of the interactions between antibodies and influenza antigens, and between virus enzymes and substrates.
The specific aims of the project are: 1. To determine the interactions involved in binding antibody to influenza virus neuraminidase (NA), to identify the size and shape of the antibody-binding surface on the NA and to determine the features which give specificity to the complementarity determining regions of anti-NA antibodies. 2. To identify the essential features of the catalytic and substrate-binding site(s) of the NA, and determine the mechanism of catalysis. Hence, inhibitors can be designed to control influenza infection by quashing NA function. 3. To obtain continuous expression of active influenza virus NA in a range of cell types using a retrovirus vector to integrate the NA gene stably into the host genome.
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