Profiling host ANP32A splicing landscapes to predict influenza A virus polymerase adaptation

Autor: Domingues, Patricia, Eletto, Davide, Magnus, Carsten, Turkington, Hannah L, Schmutz, Stefan, Zagordi, Osvaldo, Lenk, Matthias, Beer, Martin, Stertz, Silke, Hale, Benjamin G
Přispěvatelé: University of Zurich, Hale, Benjamin G
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Nature Communications, 10
Nature Communications
Nature Communications, Vol 10, Iss 1, Pp 1-12 (2019)
ISSN: 2041-1723
Popis: 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.
Nature Communications, 10
ISSN:2041-1723
Databáze: OpenAIRE