Alternative interaction sites in the influenza A virus nucleoprotein mediate viral escape from the importin-α7 mediated nuclear import pathway.
Active Transport, Cell Nucleus
Animals
Cell Nucleus
/ metabolism
Cells, Cultured
Dogs
HEK293 Cells
Humans
Influenza A Virus, H1N1 Subtype
/ genetics
Karyopherins
/ metabolism
Madin Darby Canine Kidney Cells
Mice
Mutation
Nuclear Localization Signals
Nucleoproteins
/ chemistry
Protein Binding
Viral Proteins
/ chemistry
Virus Replication
host-pathogen interaction
influenza virus
nuclear transport
protein-protein interaction
virus evolution
Journal
The FEBS journal
ISSN: 1742-4658
Titre abrégé: FEBS J
Pays: England
ID NLM: 101229646
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
05
04
2018
revised:
20
03
2019
accepted:
29
04
2019
pubmed:
3
5
2019
medline:
27
5
2020
entrez:
3
5
2019
Statut:
ppublish
Résumé
Influenza A viruses are able to adapt to restrictive conditions due to their high mutation rates. Importin-α7 is a component of the nuclear import machinery required for avian-mammalian adaptation and replicative fitness in human cells. Here, we elucidate the mechanisms by which influenza A viruses may escape replicative restriction in the absence of importin-α7. To address this question, we assessed viral evolution in mice lacking the importin-α7 gene. We show that three mutations in particular occur with high frequency in the viral nucleoprotein (NP) protein (G102R, M105K and D375N) in a specific structural area upon in vivo adaptation. Moreover, our findings suggest that the adaptive NP mutations mediate viral escape from importin-α7 requirement likely due to the utilization of alternative interaction sites in NP beyond the classical nuclear localization signal. However, viral escape from importin-α7 by mutations in NP is, at least in part, associated with reduced viral replication highlighting the crucial contribution of importin-α7 to replicative fitness in human cells.
Substances chimiques
Karyopherins
0
Nuclear Localization Signals
0
Nucleoproteins
0
Viral Proteins
0
Ipo7 protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3374-3388Subventions
Organisme : Ministerio de Ciencia e Innovación
ID : EUI2009-04018
Pays : International
Organisme : Ministerio de Ciencia e Innovación
ID : FEDER BIO2008-0205
Pays : International
Organisme : Ministerio de Ciencia e Innovación
ID : FEDER BIO2011-22568
Pays : International
Organisme : Emmy-Noether Programme
ID : GA 1575/1-1
Pays : International
Organisme : European Union
Pays : International
Organisme : Alexander von Humboldt Foundation
ID : 3.3SPA/1142463 STP-2
Pays : International
Organisme : Bundesministerium für Gesundheit
Pays : International
Organisme : Free and Hanseatic City of Hamburg
Pays : International
Informations de copyright
© 2019 Federation of European Biochemical Societies.
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