title: Highly pathogenic avian influenza virus subtype H5N1 escaping neutralization: more than HA variation.
abstract: Influenza A viruses are one of the major threats in modern health care. Novel viruses arise due to antigenic drift and antigenic shift, leading to escape from the immune system and resulting in a serious problem for disease control. In order to investigate the escape process and to enable predictions of escape, we serially passaged influenza A H5N1 virus in vitro 100 times under immune pressure. The generated escape viruses were characterized phenotypically and in detail by full-genome deep sequencing. Mutations already found in natural isolates were detected, evidencing the in vivo relevance of the in vitro-induced amino acid substitutions. Additionally, several novel alterations were triggered. Altogether, the results imply that our in vitro system is suitable to study influenza A virus evolution and that it might even be possible to predict antigenic changes of influenza A viruses circulating in vaccinated populations.
authors.affiliation: Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Höper
authors.forename: Donata
authors.initials: D
authors.lastname: Kalthoff
authors.forename: Bernd
authors.initials: B
authors.lastname: Hoffmann
authors.forename: Martin
authors.initials: M
authors.lastname: Beer
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000915:Antibody Affinity; D001483:Base Sequence; D002460:Cell Line; D002645:Chickens; D017931:DNA Primers; D005455:Fluorescent Antibody Technique; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry*; D053124:Influenza A Virus, H5N1 Subtype / Q000737:chemistry / Q000276:immunology / Q000472:pathogenicity*; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid
chemical_list: D000914:Antibodies, Viral; D017931:DNA Primers; D019267:Hemagglutinin Glycoproteins, Influenza Virus
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