This project represents the continuation of a long-term application of influenza virus genetics to the study of viral virulence and the pathogenesis and epidemiology of influenza. The model for this investigation will be the study of naturally occurring swine influenza virus hemagglutinin mutants and their derived reassortants. These mutants are dimorphic variants of current swine influenza viruses which differ pleiotropically in antigenicity and replication characteristics in chick embryos, MDCK cells and intact swine. In these studies dimorphic L and H mutants of A/NJ/11/76 H1N1 swine influenza virus and their derived reassortant viruses will be antigenically defined further by monoclonal antibodies which will be produced from mouse hybridomas by standard techniques. The reaction of L and H prototype viruses with nonspecific inhibitors and cellular receptors will be studied in order to better characterize the biological phenotype of these mutants and to develop easier methods for their identification in vitro. In collaborative studies with others a routine assay system for the differentiation of the mutants in swine will be developed. Other collaborative studies now in progress which have involved the cloning and sequencing of the hemagglutinin genes of the L and H mutant viruses will continue to establish the nucleotide and amino acid sequence difference which defines genotype of the mutants. Ultimate objectives of the study are to locate the site of amino acid change in these mutant hemagglutinin molecules which pleiotropically influence viral virulence, the minor antigenic difference which distinguishes them, and to determine the mechanism by which viral replication is so influenced by a single mutational change, and to investigate the role of this mutation in the epidemiology of swine influenza virus in its natural host. It is hoped that these studies will also aid in defining the exact nature of the receptor site on the hemagglutinin molecule.

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National Institute of Allergy and Infectious Diseases (NIAID)
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Virology Study Section (VR)
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Mount Sinai School of Medicine
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New York
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Johansson, B E; Kilbourne, E D (1992) Influenza vaccine strain selection: equivalence of two antigenically distinct haemagglutinin variants of 1989 H3N2 influenza A virus in protection of mice. Vaccine 10:603-6
Huang, T T; Malke, H; Ferretti, J J (1989) The streptokinase gene of group A streptococci: cloning, expression in Escherichia coli, and sequence analysis. Mol Microbiol 3:197-205
Johansson, B E; Bucher, D J; Pokorny, B A et al. (1989) Identification of PR8 M1 protein in influenza virus high-yield reassortants by M1-specific monoclonal antibodies. Virology 171:634-6
Johansson, B E; Bucher, D J; Kilbourne, E D (1989) Purified influenza virus hemagglutinin and neuraminidase are equivalent in stimulation of antibody response but induce contrasting types of immunity to infection. J Virol 63:1239-46
Yu, C E; Ferretti, J J (1989) Molecular epidemiologic analysis of the type A streptococcal exotoxin (erythrogenic toxin) gene (speA) in clinical Streptococcus pyogenes strains. Infect Immun 57:3715-9
Price, P M; Reichelderfer, C F; Johansson, B E et al. (1989) Complementation of recombinant baculoviruses by coinfection with wild-type virus facilitates production in insect larvae of antigenic proteins of hepatitis B virus and influenza virus. Proc Natl Acad Sci U S A 86:1453-6
Pomrenke, M E; Ferretti, J J (1989) Physical maps of the streptococcal bacteriophage A25 and C1 genomes. J Basic Microbiol 29:395-8
Huang, T T; Malke, H; Ferretti, J J (1989) Heterogeneity of the streptokinase gene in group A streptococci. Infect Immun 57:502-6
Kilbourne, E D; Easterday, B C; McGregor, S (1988) Evolution to predominance of swine influenza virus hemagglutinin mutants of predictable phenotype during single infections of the natural host. Proc Natl Acad Sci U S A 85:8098-101
Kilbourne, E D; Taylor, A H; Whitaker, C W et al. (1988) Hemagglutinin polymorphism as the basis for low- and high-yield phenotypes of swine influenza virus. Proc Natl Acad Sci U S A 85:7782-5

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