title: Substitutions T200A and E227A in the hemagglutinin of pandemic 2009 influenza A virus increase lethality but decrease transmission.
abstract: We report that swine influenza virus-like substitutions T200A and E227A in the hemagglutinin (HA) of the 2009 pandemic influenza virus alter its pathogenesis and transmission. Viral replication is increased in mammalian cells. Infected mice show increased disease as measured by weight loss and lethality. Transmission in ferrets is decreased in the presence of both substitutions, suggesting that amino acids 200T and 227E are adaptive changes in the HA of swine origin influenza viruses associated with increased transmission and decreased pathogenesis.
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Carles
authors.initials: C
authors.lastname: Martínez-Romero
authors.forename: Erik
authors.initials: E
authors.lastname: de Vries
authors.forename: Alan
authors.initials: A
authors.lastname: Belicha-Villanueva
authors.forename: Ignacio
authors.initials: I
authors.lastname: Mena
authors.forename: Donna M
authors.initials: DM
authors.lastname: Tscherne
authors.forename: Virginia L
authors.initials: VL
authors.lastname: Gillespie
authors.forename: Randy A
authors.initials: RA
authors.lastname: Albrecht
authors.forename: Cornelis A M
authors.initials: CA
authors.lastname: de Haan
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D015536:Down-Regulation; D005260:Female; D005289:Ferrets; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity*; D007251:Influenza, Human / Q000453:epidemiology / Q000401:mortality* / Q000635:transmission* / Q000821:virology; D051379:Mice; D008811:Mice, Inbred DBA; D058873:Pandemics; D015854:Up-Regulation; D014774:Virulence
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus
references.citation: J Biol Chem. 2011 Feb 18;286(7):5868-75
references.pmid: 21173148
references.citation: PLoS One. 2011;6(10):e25755
references.pmid: 21998692
references.citation: Virology. 2011 May 10;413(2):169-82
references.pmid: 21353280
references.citation: Epidemiol Rev. 1996;18(1):64-76
references.pmid: 8877331
references.citation: Emerg Infect Dis. 2010 Feb;16(2):314-7
references.pmid: 20113569
references.citation: Am J Respir Cell Mol Biol. 1996 Jan;14(1):104-12
references.pmid: 8534481
references.citation: J Virol. 2010 Nov;84(21):11219-26
references.pmid: 20739532
references.citation: J Virol. 1999 Nov;73(11):9679-82
references.pmid: 10516084
references.citation: J Clin Invest. 2011 Jan;121(1):6-13
references.pmid: 21206092
references.citation: N Engl J Med. 2009 Jun 18;360(25):2605-15
references.pmid: 19423869