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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI019084-08
Application #
3128514
Study Section
Virology Study Section (VR)
Project Start
1983-04-01
Project End
1991-03-31
Budget Start
1990-04-01
Budget End
1991-03-31
Support Year
8
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Type
Schools of Dentistry
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Gulati, Upma; Hwang, Chi-Ching; Venkatramani, Lalitha et al. (2002) Antibody epitopes on the neuraminidase of a recent H3N2 influenza virus (A/Memphis/31/98). J Virol 76:12274-80
Lee, Janis T; Air, Gillian M (2002) Contacts between influenza virus N9 neuraminidase and monoclonal antibody NC10. Virology 300:255-68
Ghate, A A; Air, G M (1999) Influenza type B neuraminidase can replace the function of type A neuraminidase. Virology 264:265-77
Pruett, P S; Air, G M (1998) Critical interactions in binding antibody NC41 to influenza N9 neuraminidase: amino acid contacts on the antibody heavy chain. Biochemistry 37:10660-70
Liu, C; Eichelberger, M C; Compans, R W et al. (1995) Influenza type A virus neuraminidase does not play a role in viral entry, replication, assembly, or budding. J Virol 69:1099-106
Nuss, J M; Air, G M (1994) Defining the requirements for an antibody epitope on influenza virus neuraminidase: how tolerant are protein epitopes? J Mol Biol 235:747-59
Zhang, H; Air, G M (1994) Expression of functional influenza virus A polymerase proteins and template from cloned cDNAS in recombinant vaccinia virus infected cells. Biochem Biophys Res Commun 200:95-101
Nuss, J M; Whitaker, P B; Air, G M (1993) Identification of critical contact residues in the NC41 epitope of a subtype N9 influenza virus neuraminidase. Proteins 15:121-32
Nuss, J M; Air, G M (1991) Transfer of the hemagglutinin activity of influenza virus neuraminidase subtype N9 into an N2 neuraminidase background. Virology 183:496-504
Air, G M; Laver, W G; Webster, R G (1990) Mechanism of antigenic variation in an individual epitope on influenza virus N9 neuraminidase. J Virol 64:5797-803

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