Profiling host ANP32A splicing landscapes to predict influenza A virus polymerase adaptation.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
30 07 2019
30 07 2019
Historique:
received:
20
10
2018
accepted:
11
07
2019
entrez:
1
8
2019
pubmed:
1
8
2019
medline:
19
12
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31363119
doi: 10.1038/s41467-019-11388-2
pii: 10.1038/s41467-019-11388-2
pmc: PMC6667478
doi:
Substances chimiques
ANP32A protein, human
0
Nuclear Proteins
0
PB2 protein, influenza virus
0
RNA-Binding Proteins
0
Viral Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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