title: Substitutions in position 222 of haemagglutinin of pandemic influenza A (H1N1) 2009 viruses in Spain.
abstract: BACKGROUND
  A change of aspartic acid (D) to glycine (G) at position 222 in the haemagglutinin (HA) protein of pandemic influenza A (H1N1) 2009 viruses was described in Norway on November 2009 with considerable frequency in fatal and severe cases. This change was detected in other countries and was related only with severe disease. Other substitutions to glutamic acid (E) or asparagine (N) at position 222 were detected among pandemic viruses but it is unclear what implications might have in terms of severity.
  
  
  OBJECTIVE
  To analyse the appearance of amino acid substitutions at position 222 in the HA protein of circulating viruses in Spain and to determine their relationships with the disease symptoms observed.
  
  
  METHODS
  Pandemic influenza A (H1N1) 2009 viruses detected in respiratory samples of 273 severe and 533 non-severe cases from different Spanish regions were selected for sequencing of a partial segment of HA1 subunit and studied to monitor substitutions at position 222.
  
  
  RESULTS
  D222G substitution was only detected in viruses from 14 severe cases (5.12%). D222E was found in viruses from 47 severe (17.21%) and from 52 non-severe cases (9.75%). D222N occurred in viruses from 3 additional severe cases (0.37%).
  
  
  CONCLUSIONS
  Appearance of D222G and D222E substitution in HA of pandemic influenza A (H1N1) viruses circulating in Spain might be related with severe respiratory disease.
authors.affiliation: Centro Nacional de Gripe-Madrid, Instituto de Salud Carlos III, Madrid, Spain. jledesmam@isciii.es
authors.forename: Juan
authors.initials: J
authors.lastname: Ledesma
authors.forename: Francisco
authors.initials: F
authors.lastname: Pozo
authors.forename: Mercedes
authors.initials: M
authors.lastname: Pérez Ruiz
authors.forename: Jose María
authors.initials: JM
authors.lastname: Navarro
authors.forename: Luis
authors.initials: L
authors.lastname: Piñeiro
authors.forename: Milagros
authors.initials: M
authors.lastname: Montes
authors.forename: Sonia
authors.initials: S
authors.lastname: Pérez Castro
authors.forename: Jonathan
authors.initials: J
authors.lastname: Suárez Fernández
authors.forename: Juan
authors.initials: J
authors.lastname: García Costa
authors.forename: Mirian
authors.initials: M
authors.lastname: Fernández
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Galán
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Cuevas
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Casas
authors.forename: Pilar
authors.initials: P
authors.lastname: Pérez Breña
mesh_terms: D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000627:therapeutic use; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics* / Q000472:pathogenicity; D007251:Influenza, Human / Q000188:drug therapy / Q000453:epidemiology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D053139:Oseltamivir / Q000627:therapeutic use; D058873:Pandemics; D017422:Sequence Analysis, DNA; D013030:Spain / Q000453:epidemiology
chemical_list: D000998:Antiviral Agents; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D053139:Oseltamivir