期刊
VIRUSES-BASEL
卷 12, 期 9, 页码 -出版社
MDPI
DOI: 10.3390/v12090920
关键词
highly pathogenic avian influenza (HPAI); low pathogenicity avian influenza (LPAI); reverse genetics; embryo culture; deep sequencing; immunohistochemistry
类别
资金
- UK Department for the Environment, Food and Rural Affairs (Defra)
- Scottish and Welsh governments [SE0793, SE2204, SE2211]
- Research and Development Internal Investment Fund (RDIIF) project [RD0055]
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(DB)), as seen in the LPAIV precursor or an SBCS representative of common H7 LPAIVs (H7N7(SB)). Passage of H7N7(DB)in chicken embryo tissues showed spontaneous evolution to a HPAIV. In contrast, deep sequencing of extracts from embryo tissues in which H7N7(SB)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.
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