title: Insertion of a multibasic cleavage site in the haemagglutinin of human influenza H3N2 virus does not increase pathogenicity in ferrets.
abstract: A multibasic cleavage site (MBCS) in the haemagglutinin (HA) protein of influenza A virus is a key determinant of pathogenicity in chickens, and distinguishes highly pathogenic avian influenza (HPAI) viruses from low pathogenic avian influenza viruses (LPAI). An MBCS has only been detected in viruses of the H5 and H7 subtypes. Here we investigated the phenotype of a human H3N2 virus with an MBCS in HA. Insertion of an MBCS in the H3N2 virus resulted in cleavage of HA and efficient replication in Madin-Darby canine kidney cells in the absence of exogenous trypsin in vitro, similar to HPAI H5N1 virus. However, studies in ferrets demonstrated that insertion of the MBCS into HA did not result in increased virus shedding, cellular host range, systemic replication or pathogenicity, as compared with wild-type virus. This study indicates that acquisition of an MBCS alone is insufficient to increase pathogenicity of a prototypical seasonal human H3N2 virus.
authors.affiliation: National Influenza Center and Department of Virology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Eefje J A
authors.initials: EJA
authors.lastname: Schrauwen
authors.affiliation: National Influenza Center and Department of Virology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Theo M
authors.initials: TM
authors.lastname: Bestebroer
authors.affiliation: Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.|National Influenza Center and Department of Virology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Munster
authors.affiliation: Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.|National Influenza Center and Department of Virology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Emmie
authors.initials: E
authors.lastname: de Wit
authors.affiliation: National Influenza Center and Department of Virology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Sander
authors.initials: S
authors.lastname: Herfst
authors.affiliation: National Influenza Center and Department of Virology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Guus F
authors.initials: GF
authors.lastname: Rimmelzwaan
authors.affiliation: National Influenza Center and Department of Virology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Albert D M E
authors.initials: ADME
authors.lastname: Osterhaus
authors.affiliation: National Influenza Center and Department of Virology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Ron A M
authors.initials: RAM
authors.lastname: Fouchier
mesh_terms: D000818:Animals; D002460:Cell Line; D004285:Dogs; D005289:Ferrets; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000737:chemistry / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D016254:Mutagenesis, Insertional; D009976:Orthomyxoviridae Infections / Q000662:veterinary* / Q000821:virology; D011499:Protein Processing, Post-Translational; D014779:Virus Replication
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus