title: Comparative analysis of avian influenza virus diversity in poultry and humans during a highly pathogenic avian influenza A (H7N7) virus outbreak.
abstract: Although increasing data have become available that link human adaptation with specific molecular changes in nonhuman influenza viruses, the molecular changes of these viruses during a large highly pathogenic avian influenza virus (HPAI) outbreak in poultry along with avian-to-human transmission have never been documented. By comprehensive virologic analysis of combined veterinary and human samples obtained during a large HPAI A (H7N7) outbreak in the Netherlands in 2003, we mapped the acquisition of human adaptation markers to identify the public health risk associated with an HPAI outbreak in poultry. Full-length hemagglutinin (HA), neuraminidase (NA), and PB2 sequencing of A (H7N7) viruses obtained from 45 human cases showed amino acid variations at different codons in HA (n=20), NA (n=23), and PB2 (n=23). Identification of the avian sources of human virus infections based on 232 farm sequences demonstrated that for each gene about 50% of the variation was already present in poultry. Polygenic accumulation and farm-to-farm spread of known virulence and human adaptation markers in A (H7N7) virus-infected poultry occurred prior to farm-to-human transmission. These include the independent emergence of HA A143T mutants, accumulation of four NA mutations, and farm-to-farm spread of virus variants harboring mammalian host determinants D701N and S714I in PB2. This implies that HPAI viruses with pandemic potential can emerge directly from poultry. Since the public health risk of an avian influenza virus outbreak in poultry can rapidly change, we recommend virologic monitoring for human adaptation markers among poultry as well as among humans during the course of an outbreak in poultry.
authors.affiliation: National Institute for Public Health and the Environment, Centre for Infectious Disease Control, P.O. Box 1, Bilthoven, Netherlands. marcel.jonges@rivm.nl
authors.forename: Marcel
authors.initials: M
authors.lastname: Jonges
authors.forename: Arnaud
authors.initials: A
authors.lastname: Bataille
authors.forename: Remko
authors.initials: R
authors.lastname: Enserink
authors.forename: Adam
authors.initials: A
authors.lastname: Meijer
authors.forename: Ron A M
authors.initials: RA
authors.lastname: Fouchier
authors.forename: Arjan
authors.initials: A
authors.lastname: Stegeman
authors.forename: Guus
authors.initials: G
authors.lastname: Koch
authors.forename: Marion
authors.initials: M
authors.lastname: Koopmans
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D004196:Disease Outbreaks; D019143:Evolution, Molecular; D014644:Genetic Variation; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics; D006801:Humans; D053126:Influenza A Virus, H7N7 Subtype / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification; D005585:Influenza in Birds / Q000453:epidemiology* / Q000821:virology*; D007251:Influenza, Human / Q000453:epidemiology* / Q000821:virology*; D020125:Mutation, Missense; D009426:Netherlands / Q000453:epidemiology; D009439:Neuraminidase / Q000235:genetics; D011200:Poultry; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics; D017422:Sequence Analysis, DNA; D014764:Viral Proteins / Q000235:genetics; D014774:Virulence
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; C057027:PB2 protein, Influenzavirus A; D014764:Viral Proteins; D012324:RNA-Dependent RNA Polymerase; C487630:NA protein, influenza A virus; D009439:Neuraminidase