The Emergence of H7N7 Highly Pathogenic Avian Influenza Virus from Low Pathogenicity Avian Influenza Virus Using an in ovo Embryo Culture Model

• Published in: Viruses Vol. 12; no. 9; p. 920
• Main Authors: Seekings, Amanda H, Howard, Wendy A, Nuñéz, Alejandro, Slomka, Marek J, Banyard, Ashley C, Hicks, Daniel, Ellis, Richard J, Nuñéz-García, Javier, Hartgroves, Lorian C, Barclay, Wendy S, Banks, Jill, Brown, Ian H
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21-08-2020; MDPI
• Subjects: Amino Acid Sequence; Amino acids; Animals; Avian flu; Birds; Chick Embryo; Chickens; deep sequencing; embryo culture; Embryos; Evolution; Evolution, Molecular; Genome, Viral - genetics; Genotypes; H7N7; Hemagglutinin Glycoproteins, Influenza Virus - genetics; highly pathogenic avian influenza (HPAI); Influenza A Virus, H7N7 Subtype - genetics; Influenza A Virus, H7N7 Subtype - metabolism; Influenza A Virus, H7N7 Subtype - pathogenicity; Influenza in Birds - pathology; Influenza in Birds - virology; low pathogenicity avian influenza (LPAI); Molecular modelling; Mutation; Outbreaks; Pathogenicity; Phenotype; Plasmids; Poultry; Poultry Diseases - pathology; Poultry Diseases - virology; reverse genetics; Survival Rate; Trypsin - metabolism; Virulence - genetics; Viruses; England; Italy; United Kingdom > UK; Australia; United States > US; reverse genetics; deep sequencing; H7N7; low pathogenicity avian influenza (LPAI); immunohistochemistry; embryo culture; highly pathogenic avian influenza (HPAI)
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v12090920

Outbreaks of highly pathogenic avian influenza virus (HPAIV) often result in the infection of millions of poultry, causing up to 100% mortality. HPAIV has been shown to emerge from low pathogenicity avian influenza virus (LPAIV) in field outbreaks. Direct evidence for the emergence of H7N7 HPAIV from a LPAIV precursor with a rare di-basic cleavage site (DBCS) was identified in the UK in 2008. The DBCS contained an additional basic amino acid compared to commonly circulating LPAIVs that harbor a single-basic amino acid at the cleavage site (SBCS). Using reverse genetics, outbreak HPAIVs were rescued with a DBCS (H7N7
), as seen in the LPAIV precursor or an SBCS representative of common H7 LPAIVs (H7N7
). Passage of H7N7
in chicken embryo tissues showed spontaneous evolution to a HPAIV. In contrast, deep sequencing of extracts from embryo tissues in which H7N7
was serially passaged showed retention of the LPAIV genotype. Thus, in chicken embryos, an H7N7 virus containing a DBCS appears naturally unstable, enabling rapid evolution to HPAIV. Evaluation in embryo tissue presents a useful approach to study AIV evolution and allows a laboratory-based dissection of molecular mechanisms behind the emergence of HPAIV.