tetano
Editor, Senior Moderator
Nat Commun. 2019 Jul 30;10(1):3396. doi: 10.1038/s41467-019-11388-2.
[h=1]Profiling host ANP32A splicing landscapes to predict influenza A virus polymerase adaptation.[/h] Domingues P[SUP]1[/SUP], Eletto D[SUP]1[/SUP], Magnus C[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Turkington HL[SUP]1[/SUP], Schmutz S[SUP]1[/SUP], Zagordi O[SUP]1[/SUP], Lenk M[SUP]4[/SUP], Beer M[SUP]4[/SUP], Stertz S[SUP]1[/SUP], Hale BG[SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Species' differences in cellular factors limit avian influenza A virus (IAV) zoonoses and human pandemics. The IAV polymerase, vPol, harbors evolutionary sites to overcome restriction and determines virulence. Here, we establish host ANP32A as a critical driver of selection, and identify host-specific ANP32A splicing landscapes that predict viral evolution. We find that avian species differentially express three ANP32A isoforms diverging in a vPol-promoting insert. ANP32As with shorter inserts interact poorly with vPol, are compromised in supporting avian-like IAV replication, and drive selection of mammalian-adaptive vPol sequences with distinct kinetics. By integrating selection data with multi-species ANP32A splice variant profiling, we develop a mathematical model to predict avian species potentially driving (swallow, magpie) or maintaining (goose, swan) mammalian-adaptive vPol signatures. Supporting these predictions, surveillance data confirm enrichment of several mammalian-adaptive vPol substitutions in magpie IAVs. Profiling host ANP32A splicing could enhance surveillance and eradication efforts against IAVs with pandemic potential.
PMID: 31363119 PMCID: PMC6667478 DOI: 10.1038/s41467-019-11388-2
Free PMC Article
[h=1]Profiling host ANP32A splicing landscapes to predict influenza A virus polymerase adaptation.[/h] Domingues P[SUP]1[/SUP], Eletto D[SUP]1[/SUP], Magnus C[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Turkington HL[SUP]1[/SUP], Schmutz S[SUP]1[/SUP], Zagordi O[SUP]1[/SUP], Lenk M[SUP]4[/SUP], Beer M[SUP]4[/SUP], Stertz S[SUP]1[/SUP], Hale BG[SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Species' differences in cellular factors limit avian influenza A virus (IAV) zoonoses and human pandemics. The IAV polymerase, vPol, harbors evolutionary sites to overcome restriction and determines virulence. Here, we establish host ANP32A as a critical driver of selection, and identify host-specific ANP32A splicing landscapes that predict viral evolution. We find that avian species differentially express three ANP32A isoforms diverging in a vPol-promoting insert. ANP32As with shorter inserts interact poorly with vPol, are compromised in supporting avian-like IAV replication, and drive selection of mammalian-adaptive vPol sequences with distinct kinetics. By integrating selection data with multi-species ANP32A splice variant profiling, we develop a mathematical model to predict avian species potentially driving (swallow, magpie) or maintaining (goose, swan) mammalian-adaptive vPol signatures. Supporting these predictions, surveillance data confirm enrichment of several mammalian-adaptive vPol substitutions in magpie IAVs. Profiling host ANP32A splicing could enhance surveillance and eradication efforts against IAVs with pandemic potential.
PMID: 31363119 PMCID: PMC6667478 DOI: 10.1038/s41467-019-11388-2
Free PMC Article