title: In vivo evaluation of pathogenicity and transmissibility of influenza A(H1N1)pdm09 hemagglutinin receptor binding domain 222 intrahost variants isolated from a single immunocompromised patient.
abstract: The influenza A(H1N1)pdm09 virus has circulated worldwide and continued to cause complicated infections and deaths. Reports have identified an increased prevalence of the hemagglutinin receptor binding domain D222G mutation in viruses isolated from individuals who have suffered such severe infections, but this association is still unclear. Virus isolated from a nasopharyngeal wash of a severely ill immunocompromised patient at the time of diagnosis contained the D222, but isolates collected later in his course from a bronchoalveolar lavage contained primarily the G222 mutation and was mixed with a minor population of D222. These clinical isolates were compared to a G222 plaque purified virus in the ferret model. The G222 predominant clinical isolate was the most pathogenic in ferrets and developed the most diversity at the 222 amino acid position during infection, suggesting that increased diversity and not a specific polymorphism at HA 222 may be important in predicting pathogenic potential.
authors.affiliation: Viral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. memolim@niaid.nih.gov
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Memoli
authors.forename: Tyler
authors.initials: T
authors.lastname: Bristol
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Proudfoot
authors.forename: A Sally
authors.initials: AS
authors.lastname: Davis
authors.forename: Eleca J
authors.initials: EJ
authors.lastname: Dunham
authors.forename: Jeffery K
authors.initials: JK
authors.lastname: Taubenberger
mesh_terms: D000818:Animals; D005289:Ferrets; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016867:Immunocompromised Host; D053118:Influenza A Virus, H1N1 Subtype / Q000145:classification / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D007251:Influenza, Human / Q000378:metabolism / Q000473:pathology / Q000635:transmission / Q000821:virology*; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010802:Phylogeny; D011991:Receptors, Virus / Q000378:metabolism
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011991:Receptors, Virus