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Hemagglutinin reassortment dynamics of the zoonotic H9N2 avian influenza virusMannsverk, Steinar S January 2020 (has links)
The H9N2 avian influenza virus (AIV) has emerged, spread and established itself in poultry globally, in just under 30 years. During this time, multiple reassortants of H9N2 with increased zoonotic potential have been isolated in poultry and humans, causing a major threat to the economy and global health. Curiously, H9N2 appears to be compatible with multiple Hemagglutinin (HA) and Neuraminidase subtypes, in nature. Here, the aim was to investigate the HA reassortment dynamics of the poultry adapted H9N2 AIV, in a laboratory setting. Firstly, HA subtypes from wild bird isolates were cloned, before being co-transfected with the backbone of a chicken H9N2 AIV. The rescued H9N2 reassortants were titred on cells before the replication kinetics of a subset of the HA reassortants was assessed. The cDNA sequence of seven HA subtypes induced extensive recombination in E. coli, but ultimately ten out of eleven available HA subtypes were successfully cloned. Further, the chicken H9N2 AIV was compatible with all ten HA subtypes, producing infectious viral particles after co-transfection. However, all HA reassortants displayed decreased replicative fitness in MDCK-2 cells, compared to the wild-type virus. Interestingly, HA subtypes with similar genotypes cluster into distinct HA clades and groups, but these HA clades did not correlate with the replicative fitness of the reassortants. This study suggests that poultry adapted H9N2 AIV is compatible with many HA subtypes, highlighting the importance of reducing its spread in poultry, to reduce reassortment opportunities.
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