In the past few years, considerable progress has been made in our understanding of the sequence and structure of the genes and gene products of influenza viruses. Both surface glycoproteins of the virus that are important in antigenic variation have been crystallized and the three-dimensional structure determined by X-ray crystallography. Despite these achievements, influenza viruses still continue to appear that can cause high mortality in animal species - most recently in chickens. Influenza in humans has been relatively mild over the past decade, causing only modest increases in morbidity and mortality, but the potential exists for a virus of high pathogenicity to occur in humans. There are clearly gaps in our knowledge of influenza virus and the specific aims are the following: 1) To define the antigenic areas on the neuraminidase of influenza virus, especially the N9 subtype that possesses both hemagglutinating and enzyme activity and is phenotypically similar to the HN protein of paramyxoviruses. 2) To define the molecular basis of the biological functions of the hemagglutinin (HA), including the antigenic sites, receptor binding site and fusion peptide and relate them to influenza virus variability. 3) To determine how antigenic drift occurs in nature in the presence of a polyclonal antibody population and whether it can reach an evolutionary endpoint. 4) To define the molecular changes that permit an influenza virus to become virulent. The outbreak of H5N2 influenza in chickens in Pennsylvania that """"""""acquired"""""""" virulence offers a natural system for such studies. Recent advances in sequencing methods and monoclonal antibodies now permit analysis of the important outstanding biological questions such as the origin of influenza viruses, the molecular basis of virulence and how antigenic drift occurs in nature.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI008831-18
Application #
3124457
Study Section
Virology Study Section (VR)
Project Start
1975-02-01
Project End
1990-01-31
Budget Start
1986-02-01
Budget End
1987-01-31
Support Year
18
Fiscal Year
1986
Total Cost
Indirect Cost
Name
St. Jude Children's Research Hospital
Department
Type
DUNS #
067717892
City
Memphis
State
TN
Country
United States
Zip Code
38105
Caver, T E; Lockey, T D; Srinivas, R V et al. (1999) A novel vaccine regimen utilizing DNA, vaccinia virus and protein immunizations for HIV-1 envelope presentation. Vaccine 17:1567-72
Scholtissek, C; Quack, G; Klenk, H D et al. (1998) How to overcome resistance of influenza A viruses against adamantane derivatives. Antiviral Res 37:83-95
Rohm, C; Zhou, N; Suss, J et al. (1996) Characterization of a novel influenza hemagglutinin, H15: criteria for determination of influenza A subtypes. Virology 217:508-16
Webster, R G; Fynan, E F; Santoro, J C et al. (1994) Protection of ferrets against influenza challenge with a DNA vaccine to the haemagglutinin. Vaccine 12:1495-8
Connor, R J; Kawaoka, Y; Webster, R G et al. (1994) Receptor specificity in human, avian, and equine H2 and H3 influenza virus isolates. Virology 205:17-23
Lai, A C; Lin, Y P; Powell, D G et al. (1994) Genetic and antigenic analysis of the influenza virus responsible for the 1992 Hong Kong equine influenza epizootic. Virology 204:673-9
Saito, T; Horimoto, T; Kawaoka, Y et al. (1994) Emergence of a potentially pathogenic H5N2 influenza virus in chickens. Virology 201:277-84
Malby, R L; Tulip, W R; Harley, V R et al. (1994) The structure of a complex between the NC10 antibody and influenza virus neuraminidase and comparison with the overlapping binding site of the NC41 antibody. Structure 2:733-46
Kortt, A A; Malby, R L; Caldwell, J B et al. (1994) Recombinant anti-sialidase single-chain variable fragment antibody. Characterization, formation of dimer and higher-molecular-mass multimers and the solution of the crystal structure of the single-chain variable fragment/sialidase complex. Eur J Biochem 221:151-7
Saito, T; Taylor, G; Laver, W G et al. (1994) Antigenicity of the N8 influenza A virus neuraminidase: existence of an epitope at the subunit interface of the neuraminidase. J Virol 68:1790-6

Showing the most recent 10 out of 89 publications