Loss of function of the influenza A virus NS1 protein promotes apoptosis but this is not due to a failure to activate phosphatidylinositol 3-kinase (PI3K)

David Jackson, Marian J. Killip, Caroline S. Galloway, Rupert J. Russell, Richard E. Randall

Research output: Contribution to journalArticlepeer-review

Abstract

A panel of influenza A viruses encoding mutant NS1 proteins was created in which a number of NS1 functions, including interactions with dsRNA, PI3K, CPSF30 and PKR, were inhibited. Surprisingly, given previous reports that NS1 activates PI3K to prevent apoptosis, the mutant viruses rUd-Y89F and rUd-P164/7A that fail to activate PI3K did not induce any more apoptosis than wild-type virus in MRC-5 and A549 cells, even though these cells are highly sensitive to inducers of apoptosis. Induction of cell death by the apoptogenic rUd-184-8(P) virus could not be prevented by serum-mediated activation of PI3K/Akt. Neither infection of MRC-5 or A549 cells with wild-type virus nor constitutive expression of NS1 prevented cell death caused by apoptosis inducers, suggesting that NS1 is not directly anti-apoptotic. Our data suggest that the loss of a functionally intact NS1 protein promotes apoptosis, but this is not due to an inability to activate PI3K. (C) 2009 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)94-105
Number of pages12
JournalVirology
Volume396
Issue number1
DOIs
Publication statusPublished - 5 Jan 2010

Keywords

  • Influenza A virus
  • Reverse genetics
  • NS1
  • Apoptosis
  • PI3K
  • DOUBLE-STRANDED-RNA
  • AIRWAY EPITHELIAL-CELLS
  • PRE-MESSENGER-RNAS
  • INFECTED-CELLS
  • RIG-I
  • MITOCHONDRIAL PROTEIN
  • ANTIVIRAL RESPONSES
  • SIGNALING PATHWAY
  • UBIQUITIN LIGASE
  • DEATH APOPTOSIS

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