Effects of mutations in the effector domain of influenza A virus NS1 protein 06 Biological Sciences 0601 Biochemistry and Cell Biology

Carina F. Pereira, Helen M. Wise, Dominic Kurian, Rute M. Pinto, Maria J. Amorim, Andrew C. Gill, Paul Digard

Research output: Contribution to journalArticle

Abstract

Objective: The multifunctional NS1 protein of influenza A virus has roles in antagonising cellular innate immune responses and promoting viral gene expression. To better understand the interplay between these functions, we tested the effects of NS1 effector domain mutations known to affect homo-dimerisation or interactions with cellular PI3 kinase or Trim25 on NS1 ability to promote nuclear export of viral mRNAs. Results: The NS1 dimerisation mutant W187R retained the functions of binding cellular NXF1 as well as stabilising NXF1 interaction with viral segment 7 mRNAs and promoting their nuclear export. Two PI3K-binding mutants, NS1 Y89F and Y89A still bound NXF1 but no longer promoted NXF1 interactions with segment 7 mRNA or its nuclear export. The Trim25-binding mutant NS1 E96A/E97A bound NXF1 and supported NXF1 interactions with segment 7 mRNA but no longer supported mRNA nuclear export. Analysis of WT and mutant NS1 interaction partners identified hsp70 as specifically binding to NS1 E96A/E97A. Whilst these data suggest the possibility of functional links between NS1's effects on intracellular signalling and its role in viral mRNA nuclear export, they also indicate potential pleiotropic effects of the NS1 mutations; in the case of E96A/E97A possibly via disrupted protein folding leading to chaperone recruitment.

Original languageEnglish
Article number673
JournalBMC Research Notes
Volume11
DOIs
Publication statusPublished - 18 Sep 2018

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Cytology
Biochemistry
Biological Science Disciplines
Cell Nucleus Active Transport
Cell Biology
Messenger RNA
Mutation
Dimerization
Phosphatidylinositol 3-Kinases
Protein folding
Viral Genes
Protein Folding
Innate Immunity
Gene expression
Cellular Immunity
influenza virus INS1 protein
Gene Expression

Keywords

  • Influenza A virus
  • NS1
  • Nuclear export
  • PI3K
  • RIG-I
  • Trim25

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Pereira, Carina F. ; Wise, Helen M. ; Kurian, Dominic ; Pinto, Rute M. ; Amorim, Maria J. ; Gill, Andrew C. ; Digard, Paul. / Effects of mutations in the effector domain of influenza A virus NS1 protein 06 Biological Sciences 0601 Biochemistry and Cell Biology. In: BMC Research Notes. 2018 ; Vol. 11.
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Effects of mutations in the effector domain of influenza A virus NS1 protein 06 Biological Sciences 0601 Biochemistry and Cell Biology. / Pereira, Carina F.; Wise, Helen M.; Kurian, Dominic; Pinto, Rute M.; Amorim, Maria J.; Gill, Andrew C.; Digard, Paul.

In: BMC Research Notes, Vol. 11, 673, 18.09.2018.

Research output: Contribution to journalArticle

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