title: H9 avian influenza reassortant with engineered polybasic cleavage site displays a highly pathogenic phenotype in chicken.
abstract: In the field, highly pathogenic avian influenza viruses (HPAIV) originate from low-pathogenic strains of the haemagglutinin (HA) serotypes H5 and H7 that have acquired a polybasic HA cleavage site. This observation suggests the presence of a cryptic virulence potential of H5 and H7 low-pathogenic avian influenza viruses (LPAIV). Among all other LPAIV, the H9N2 strains are of particular relevance as they have become widespread across many countries in several avian species and have been transmitted to humans. To assess the potential of these strains to transform into an HPAIV, we introduced a polybasic cleavage site into the HA of a contemporary H9N2 isolate. Whereas the engineered polybasic HA cleavage site mutant remained a low-pathogenic strain like its parent virus, a reassortant expressing the modified H9 HA with engineered polybasic cleavage site and all the other genes from an H5N1 HPAIV became highly pathogenic in chicken with an intravenous pathogenicity index of 1.23. These results suggest that an HPAIV with a subtype other than H5 or H7 would only emerge under conditions where the HA gene could acquire a polybasic cleavage site and the other viral genes carry additional virulence determinants.
authors.affiliation: Friedrich Loeffler Institute, Institute of Molecular Biology, Greifswald-Insel Riems, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Gohrbandt
authors.affiliation: Friedrich Loeffler Institute, Institute of Molecular Biology, Greifswald-Insel Riems, Germany.
authors.forename: Jutta
authors.initials: J
authors.lastname: Veits
authors.affiliation: Friedrich Loeffler Institute, Institute of Infectology, Greifswald-Insel Riems, Germany.
authors.forename: Angele
authors.initials: A
authors.lastname: Breithaupt
authors.affiliation: Friedrich Loeffler Institute, Institute of Molecular Biology, Greifswald-Insel Riems, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Hundt
authors.affiliation: Friedrich Loeffler Institute, Institute of Infectology, Greifswald-Insel Riems, Germany.
authors.forename: Jens P
authors.initials: JP
authors.lastname: Teifke
authors.affiliation: Friedrich Loeffler Institute, Institute of Molecular Biology, Greifswald-Insel Riems, Germany.
authors.forename: Olga
authors.initials: O
authors.lastname: Stech
authors.affiliation: Friedrich Loeffler Institute, Institute of Molecular Biology, Greifswald-Insel Riems, Germany.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Mettenleiter
authors.affiliation: Friedrich Loeffler Institute, Institute of Molecular Biology, Greifswald-Insel Riems, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Stech
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D002460:Cell Line; D002645:Chickens; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D053127:Influenza A Virus, H9N2 Subtype / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity*; D005585:Influenza in Birds / Q000821:virology*; D015202:Protein Engineering; D011499:Protein Processing, Post-Translational; D016865:Reassortant Viruses / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D013047:Specific Pathogen-Free Organisms; D014774:Virulence
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; C109963:hemagglutinin, avian influenza A virus