The pH of Activation of the Hemagglutinin Protein Regulates H5N1 Influenza Virus Pathogenicity and Transmissibility in Ducks

• DOI: 10.1128/jvi.02069-09
• Publication Date: 2009-11-19T01:50:35Z
• Authors: Mark L. Reed; Olga A. Bridges; Patrick Seiler; Jeong-Ki Kim; Hui-Ling Yen; Rachelle Salomon; Elena A. Govorkova; Robert G. Webster; Charles J. Russell
• Keywords: Recombination, Genetic; 0301 basic medicine; Hemagglutinin Glycoproteins; 570; 0303 health sciences; Influenza A Virus, H5N1 Subtype; Bird Diseases; Hemagglutinin Glycoproteins, Influenza Virus; Influenza A Virus, H5n1 Subtype - Genetics - Pathogenicity; Hydrogen-Ion Concentration; Bird Diseases - Transmission; Membrane Fusion; Recombination; Influenza Virus - Genetics - Metabolism; 3. Good health; 03 medical and health sciences; Ducks; Genetic; Hemagglutinin Glycoproteins, Influenza Virus - Genetics - Metabolism; Mutation; Influenza A Virus; Animals; H5n1 Subtype - Genetics - Pathogenicity

While the molecular mechanism of membrane fusion by influenza virus hemagglutinin (HA) protein has been studied extensively in vitro, role acid-dependent HA activation replication, pathogenesis, and transmission vivo not characterized. To investigate biological significance pH protein, we compared properties four recombinant viruses with altered acid stability to those wild-type A/chicken/Vietnam/C58/04 (H5N1) vitro mallards. Membrane was activated at 5.9. Wild-type had a calculated environmental persistence 62 days caused extensive morbidity, mortality, shedding, An N114K mutation that increased 0.5 unit resulted decreased genetic stability, stability. Changes +0.4 -0.5 Y23H K58I mutations, respectively, reduced weight loss, H24Q 0.3 clinical symptoms, shedding similar wild type. However, HA-H24(1)Q shed more into drinking water persisted longer environment. The H5 plays key propagation H5N1 ducks may be novel factor ecology viruses. data also demonstrate neuraminidase activity increases vitro.