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 |
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Přispěvatelé: | University of Zurich, Hale, Benjamin G |
Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
10028 Institute of Medical Virology
Science RNA Splicing 610 Medicine & health 1600 General Chemistry Virus Replication Virus-host interactions Article Birds Viral Proteins Influenza A Virus H1N1 Subtype 1300 General Biochemistry Genetics and Molecular Biology Influenza Human Animals Humans Computational models Amino Acid Sequence lcsh:Science Viral evolution Nuclear Proteins RNA-Binding Proteins 3100 General Physics and Astronomy Influenza A virus Influenza in Birds 570 Life sciences biology lcsh:Q Influenza virus Chickens Protein Binding |
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 |
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