Giuseppe
Emeritus
J Virol. 2009 Nov 18. [Epub ahead of print]
The pH of Activation of the Hemagglutinin Protein Regulates H5N1 Influenza Virus Pathogenicity and Transmissibility in Ducks.
Reed ML, Bridges OA, Seiler P, Kim JK, Yen HL, Salomon R, Govorkova EA, Webster RG, Russell CJ. - Division of Virology, Department of Infectious Diseases, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105-3678; and Department of Molecular Sciences, University of Tennessee, Memphis, Tennessee 38163.
While the molecular mechanism of membrane fusion by the influenza virus hemagglutinin (HA) protein has been studied extensively in vitro, the role of acid-dependent HA protein activation in virus replication, pathogenesis, and transmission in vivo has not been characterized. To investigate the biological significance of the pH of activation of the HA protein, we compared the properties of four recombinant viruses with altered HA protein acid stability to those of wild-type A/chicken/Vietnam/C58/04 (H5N1) in vitro and in mallards. Membrane fusion by wild-type was activated at pH 5.9. Wild-type virus had a calculated environmental persistence of 62 days and caused extensive morbidity, mortality, shedding, and transmission in mallards. An N1142K mutation that increased the pH of HA activation by 0.5 units resulted in decreased replication, genetic stability, and environmental stability. Changes of +0.4 and -0.5 units in the pH of activation by Y231H and K582I mutations, respectively, reduced weight loss, mortality, shedding, and transmission in mallards. An H241Q mutation that decreased the pH of activation by 0.3 units resulted in weight loss, mortality, clinical symptoms, and shedding similar to wild-type. However, the HA-H241Q virus was shed more extensively into drinking water and persisted longer in the environment. The pH of activation of the H5 HA protein plays a key role in the propagation of H5N1 influenza viruses in ducks and may be a novel molecular factor in the ecology of influenza viruses. The data also demonstrates that H5N1 neuraminidase activity increases the pH of activation of the HA protein in vitro.
PMID: 19923184 [PubMed - as supplied by publisher]
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The pH of Activation of the Hemagglutinin Protein Regulates H5N1 Influenza Virus Pathogenicity and Transmissibility in Ducks.
Reed ML, Bridges OA, Seiler P, Kim JK, Yen HL, Salomon R, Govorkova EA, Webster RG, Russell CJ. - Division of Virology, Department of Infectious Diseases, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105-3678; and Department of Molecular Sciences, University of Tennessee, Memphis, Tennessee 38163.
While the molecular mechanism of membrane fusion by the influenza virus hemagglutinin (HA) protein has been studied extensively in vitro, the role of acid-dependent HA protein activation in virus replication, pathogenesis, and transmission in vivo has not been characterized. To investigate the biological significance of the pH of activation of the HA protein, we compared the properties of four recombinant viruses with altered HA protein acid stability to those of wild-type A/chicken/Vietnam/C58/04 (H5N1) in vitro and in mallards. Membrane fusion by wild-type was activated at pH 5.9. Wild-type virus had a calculated environmental persistence of 62 days and caused extensive morbidity, mortality, shedding, and transmission in mallards. An N1142K mutation that increased the pH of HA activation by 0.5 units resulted in decreased replication, genetic stability, and environmental stability. Changes of +0.4 and -0.5 units in the pH of activation by Y231H and K582I mutations, respectively, reduced weight loss, mortality, shedding, and transmission in mallards. An H241Q mutation that decreased the pH of activation by 0.3 units resulted in weight loss, mortality, clinical symptoms, and shedding similar to wild-type. However, the HA-H241Q virus was shed more extensively into drinking water and persisted longer in the environment. The pH of activation of the H5 HA protein plays a key role in the propagation of H5N1 influenza viruses in ducks and may be a novel molecular factor in the ecology of influenza viruses. The data also demonstrates that H5N1 neuraminidase activity increases the pH of activation of the HA protein in vitro.
PMID: 19923184 [PubMed - as supplied by publisher]
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