Projects per year
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 language | English |
---|---|
Pages (from-to) | 94-105 |
Number of pages | 12 |
Journal | Virology |
Volume | 396 |
Issue number | 1 |
DOIs | |
Publication status | Published - 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
Fingerprint
Dive into the research topics of '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)'. Together they form a unique fingerprint.Projects
- 1 Finished
-
Virus NS1 - PI3 G0601126: Studies on the interaction of influenza virus NS1 protein with cellular P13-kinase
Randall, R. E. (PI)
1/10/07 → 31/12/10
Project: Standard