mutations in h5n1 influenza virus hemagglutinin that confer binding to human tracheal airway epithelium突变h5n1流感病毒血凝素赋予人类气管气道上皮细胞结合.pdfVIP

Mutations in H5N1 Influenza Virus Hemagglutinin that Confer Binding to Human Tracheal Airway Epithelium 1. 1. 2 3 3 Guadalupe Ayora-Talavera , Holly Shelton , Margaret A. Scull , Junyuan Ren , Ian M. Jones , 2 1 Raymond J. Pickles , Wendy S. Barclay * 1 Department of Virology, Imperial College London, London, United Kingdom, 2 Cystic Fibrosis/Pulmonary Research and Treatment Center, Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America, 3 School of Biological Sciences, University of Reading, Whiteknights, Reading, United Kingdom Abstract The emergence in 2009 of a swine-origin H1N1 influenza virus as the first pandemic of the 21st Century is a timely reminder of the international public health impact of influenza viruses, even those associated with mild disease. The widespread distribution of highly pathogenic H5N1 influenza virus in the avian population has spawned concern that it may give rise to a human influenza pandemic. The mortality rate associated with occasional human infection by H5N1 virus approximates 60%, suggesting that an H5N1 pandemic would be devastating to global health and economy. To date, the H5N1 virus has not acquired the propensity to transmit efficiently between humans. The reasons behind this are unclear, especially given the high mutation rate associated with influenza virus replication. Here we used a panel of recombinant H5 hemagglutinin (HA) variants to demonstrate the potential for H5 HA to bind human airway epithelium, the predominant target tissue for influenza virus infection and spread. While parental H5 HA exhibited li