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Elife. 2019 Apr 30;8. pii: e45079. doi: 10.7554/eLife.45079.
Comprehensive mapping of adaptation of the avian influenza polymerase protein PB2 to humans.
Soh YS1,2, Moncla LH2,3, Eguia R1, Bedford T2,3, Bloom JD1,2,4.
Author information
Abstract
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.
KEYWORDS:
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
Comprehensive mapping of adaptation of the avian influenza polymerase protein PB2 to humans.
Soh YS1,2, Moncla LH2,3, Eguia R1, Bedford T2,3, Bloom JD1,2,4.
Author information
Abstract
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.
KEYWORDS:
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