Abstract
Adaptation of PB2 protein is important for the establishment of avian influenza viruses in mammalian hosts. Here, we identify I292V as the prevalent mutation in PB2 of circulating avian H9N2 and pandemic H1N1 viruses. The same dominant PB2 mutation is also found in most human isolates of emergent avian H7N9 and H10N8 viruses. In human cells, PB2-292V in H9N2 virus has the combined ability of conferring higher viral polymerase activity and stronger attenuation of IFN-β induction than that of its predecessor PB2-292I. IFN-β attenuation is accompanied by higher binding affinity of PB2-292V for host mitochondrial antiviral signalling protein, an important intermediary protein in the induction of IFN-β. In the mouse in vivo model, PB2-292V mutation increases H9N2 virus replication with ensuing increase in disease severity. Collectively, PB2-292V is a new mammalian adaptive marker that promotes H9N2 virus replication in mammalian hosts with the potential to improve transmission from birds to humans.
Highlights
Avian H9N2 influenza viruses circulate worldwide and are endemic in terrestrial avian species [1, 2]
Current avian H9N2 influenza virus and its reassortants exhibit a growing trend toward enhanced human infection capacity; adaptive mutations of PB2 protein have been demonstrated to be important in host adaptation [10, 16,17,18, 24, 25]
We further compared the prevalence of PB2-292V in H9N2, novel H7N9 and H10N8 viruses isolated from avian and human hosts (Fig. 1b)
Summary
Avian H9N2 influenza viruses circulate worldwide and are endemic in terrestrial avian species [1, 2]. They are transmitted to mammalian species, including humans and pigs [3, 4]. Since 2013, two novel reassortants, H7N9 and H10N8 viruses, whose internal genes were derived from prevailing H9N2 virus, have caused regular human infections and prompted serious public health concerns [6,7,8]. Current avian H9N2 viruses and their reassortants exhibit increasing transmissibility in humans, indicating that their shared H9N2-derived internal genes are progressively adapting in human replication
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