title: Acquisition of a polybasic hemagglutinin cleavage site by a low-pathogenic avian influenza virus is not sufficient for immediate transformation into a highly pathogenic strain.
abstract: Highly pathogenic avian influenza viruses (HPAIV) differ from all other strains by a polybasic cleavage site in their hemagglutinin. All these HPAIV share the H5 or H7 subtype. In order to investigate whether the acquisition of a polybasic cleavage site by an avirulent avian influenza virus strain with a hemagglutinin other than H5 or H7 is sufficient for immediate transformation into an HPAIV, we adapted the hemagglutinin cleavage site of A/Duck/Ukraine/1/1963 (H3N8) to that of the HPAIV A/Chicken/Italy/8/98 (H5N2), A/Chicken/HongKong/220/97 (H5N1), or A/Chicken/Germany/R28/03 (H7N7) and generated the recombinant wild-type and cleavage site mutants. In contrast to the wild type, multicycle replication of these mutants in tissue culture was demonstrated by positive plaque assays and viral multiplication in the absence of exogenous trypsin. Therefore, in vitro all cleavage site mutants resemble an HPAIV. However, in chicken they did not exhibit high pathogenicity, although they could be reisolated from cloacal swabs to some extent, indicating enhanced replication in vivo. These results demonstrate that beyond the polybasic hemagglutinin cleavage site, the virulence of HPAIV in chicken is based on additional pathogenicity determinants within the hemagglutinin itself or in the other viral proteins. Taken together, these observations support the notion that acquisition of a polybasic hemagglutinin cleavage site by an avirulent strain with a non-H5/H7 subtype is only one among several alterations necessary for evolution into an HPAIV.
authors.affiliation: Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany.
authors.forename: Olga
authors.initials: O
authors.lastname: Stech
authors.forename: Jutta
authors.initials: J
authors.lastname: Veits
authors.forename: Siegfried
authors.initials: S
authors.lastname: Weber
authors.forename: Daniela
authors.initials: D
authors.lastname: Deckers
authors.forename: Diana
authors.initials: D
authors.lastname: Schröer
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Vahlenkamp
authors.forename: Angele
authors.initials: A
authors.lastname: Breithaupt
authors.forename: Jens
authors.initials: J
authors.lastname: Teifke
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Mettenleiter
authors.forename: Jürgen
authors.initials: J
authors.lastname: Stech
mesh_terms: D000818:Animals; D002460:Cell Line; D002645:Chickens / Q000821:virology; D004285:Dogs; D019143:Evolution, Molecular; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000378:metabolism*; D053123:Influenza A Virus, H3N8 Subtype / Q000145:classification / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D053124:Influenza A Virus, H5N1 Subtype / Q000378:metabolism / Q000472:pathogenicity; D053125:Influenza A Virus, H5N2 Subtype / Q000378:metabolism / Q000472:pathogenicity; D053126:Influenza A Virus, H7N7 Subtype / Q000378:metabolism / Q000472:pathogenicity; D005585:Influenza in Birds / Q000821:virology*; D009154:Mutation / Q000235:genetics; D019076:Transgenes / Q000235:genetics
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus