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Journal of Virology, June 2009, p. 5864-5868, Vol. 83, No. 11
0022-538X/09/$08.00+0     doi:10.1128/JVI.02649-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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{triangledown}

Olga Stech, Jutta Veits, Siegfried Weber, Daniela Deckers, Diana Schröer, Thomas W. Vahlenkamp, Angele Breithaupt, Jens Teifke, Thomas C. Mettenleiter, and Jürgen Stech*

Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Südufer 10, 17493 Greifswald-Insel Riems, Germany

Received 23 December 2008/ Accepted 17 March 2009

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.

* Corresponding author. Mailing address: Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Südufer 10, 17493 Greifswald-Insel Riems, Germany. Phone: 49 383517237. Fax: 49 383517275. E-mail: juergen.stech{at}fli.bund.de

{triangledown} Published ahead of print on 18 March 2009.

Journal of Virology, June 2009, p. 5864-5868, Vol. 83, No. 11
0022-538X/09/$08.00+0     doi:10.1128/JVI.02649-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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