tetano
Editor, Senior Moderator
Elife. 2019 Apr 30;8. pii: e45079. doi: 10.7554/eLife.45079.
[h=1]Comprehensive mapping of adaptation of the avian influenza polymerase protein PB2 to humans.[/h] Soh YS[SUP]1,[/SUP][SUP]2[/SUP], Moncla LH[SUP]2,[/SUP][SUP]3[/SUP], Eguia R[SUP]1[/SUP], Bedford T[SUP]2,[/SUP][SUP]3[/SUP], Bloom JD[SUP]1,[/SUP][SUP]2,[/SUP][SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Viruses like influenza are infamous for their ability to adapt to new hosts. Retrospective studies of natural zoonoses and passaging in the lab have identified a modest number of host-adaptive mutations. However, it is unclear if these mutations represent all ways that influenza can adapt to a new host. Here we take a prospective approach to this question by completely mapping amino-acid mutations to the avian influenza virus polymerase protein PB2 that enhance growth in human cells. We identify numerous previously uncharacterized human-adaptive mutations. These mutations cluster on PB2's surface, highlighting potential interfaces with host factors. Some previously uncharacterized adaptive mutations occur in avian-to-human transmission of H7N9 influenza, showing their importance for natural virus evolution. But other adaptive mutations do not occur in nature because they are inaccessible via single-nucleotide mutations. Overall, our work shows how selection at key molecular surfaces combines with evolutionary accessibility to shape viral host adaptation.
? 2019, Soh et al.
[h=4]KEYWORDS:[/h] PB2; cross-species transmission; deep mutational scanning; epidemiology; global health; host jump; infectious disease; influenza; microbiology; pandemic
PMID: 31038123 PMCID: PMC6491042 DOI: 10.7554/eLife.45079
Free PMC Article
[h=1]Comprehensive mapping of adaptation of the avian influenza polymerase protein PB2 to humans.[/h] Soh YS[SUP]1,[/SUP][SUP]2[/SUP], Moncla LH[SUP]2,[/SUP][SUP]3[/SUP], Eguia R[SUP]1[/SUP], Bedford T[SUP]2,[/SUP][SUP]3[/SUP], Bloom JD[SUP]1,[/SUP][SUP]2,[/SUP][SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Viruses like influenza are infamous for their ability to adapt to new hosts. Retrospective studies of natural zoonoses and passaging in the lab have identified a modest number of host-adaptive mutations. However, it is unclear if these mutations represent all ways that influenza can adapt to a new host. Here we take a prospective approach to this question by completely mapping amino-acid mutations to the avian influenza virus polymerase protein PB2 that enhance growth in human cells. We identify numerous previously uncharacterized human-adaptive mutations. These mutations cluster on PB2's surface, highlighting potential interfaces with host factors. Some previously uncharacterized adaptive mutations occur in avian-to-human transmission of H7N9 influenza, showing their importance for natural virus evolution. But other adaptive mutations do not occur in nature because they are inaccessible via single-nucleotide mutations. Overall, our work shows how selection at key molecular surfaces combines with evolutionary accessibility to shape viral host adaptation.
? 2019, Soh et al.
[h=4]KEYWORDS:[/h] PB2; cross-species transmission; deep mutational scanning; epidemiology; global health; host jump; infectious disease; influenza; microbiology; pandemic
PMID: 31038123 PMCID: PMC6491042 DOI: 10.7554/eLife.45079
Free PMC Article