PMID- 21430412
OWN - NLM
STAT- MEDLINE
DCOM- 20110805
LR  - 20191210
IS  - 1423-0313 (Electronic)
IS  - 0031-7012 (Linking)
VI  - 87
IP  - 3-4
DP  - 2011
TI  - Possible role of phosphoinositide-3-kinase in Mx1 protein translation and 
      antiviral activity of interferon-omega-stimulated HeLa cells.
PG  - 224-31
LID - 10.1159/000324536 [doi]
AB  - Interferon omega (IFN-omega), a cytokine released during innate immune activation, is 
      well known for promoting direct antiviral responses; however, the possible signal 
      pathways that are initiated by IFN-omega binding to the type I IFN receptors have not 
      been fully studied. Here, we provide evidence that activation of 
      phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) signaling plays a pivotal 
      role in the generation of IFN-omega-mediated biological responses. We found that 
      LY294002 (PI3K inhibitor)-attenuated antiviral activities are induced by IFN-omega 
      treatment. Although such effects of LY294002 are unrelated to regulatory 
      activities on IFN-omega-dependent Mx1 (myxovirus resistance 1) or Mx2 gene 
      transcriptional regulation, translation of Mx1 protein, which was known as a key 
      mediator of cell-autonomous antiviral resistance, was significantly reduced by 
      PI3K inhibition. Further studies showed that PI3K inhibition using LY294002 leads 
      to a decrease in PI3K substrate Akt and mitogen-activated protein kinase 
      extracellular signal-regulated kinase and p38 phosphorylation/activation. In 
      addition, although LY294002 was not able to reduce STAT1 activation, we found 
      that the mammalian target of rapamycin (mTOR)/p70 S6 kinase pathway was 
      significantly attenuated by inhibition of the PI3K/Akt signaling pathway. These 
      results indicate that the PI3K/Akt pathway is a common and central integrator for 
      antiviral responses in IFN-omega signaling via its regulatory effects on mTOR that 
      are required for initiation of mRNA translation of Mx genes.
CI  - Copyright (c) 2011 S. Karger AG, Basel.
FAU - Seo, Youngjun
AU  - Seo Y
AD  - Advanced Therapy Products Research Division, National Institute of Food and Drug 
      Safety Evaluation, Korea Food and Drug Administration, Chungcheongbuk-do, 
      Republic of Korea.
FAU - Kim, Mihee
AU  - Kim M
FAU - Choi, Minjoung
AU  - Choi M
FAU - Kim, Sunhee
AU  - Kim S
FAU - Park, Kidae
AU  - Park K
FAU - Oh, Ilung
AU  - Oh I
FAU - Chung, Seungtae
AU  - Chung S
FAU - Suh, Hongwon
AU  - Suh H
FAU - Hong, Seunghwa
AU  - Hong S
FAU - Park, Suenie
AU  - Park S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110325
PL  - Switzerland
TA  - Pharmacology
JT  - Pharmacology
JID - 0152016
RN  - 0 (Antiviral Agents)
RN  - 0 (Interferon Type I)
RN  - 0 (Myxovirus Resistance Proteins)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (interferon omega 1)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
SB  - IM
MH  - Animals
MH  - Antiviral Agents/*pharmacology
MH  - Blotting, Western
MH  - Cell Culture Techniques
MH  - Chlorocebus aethiops
MH  - Cytopathogenic Effect, Viral/drug effects
MH  - Encephalomyocarditis virus/drug effects
MH  - GTP-Binding Proteins/*genetics
MH  - HeLa Cells
MH  - Humans
MH  - Interferon Type I/*pharmacology
MH  - Myxovirus Resistance Proteins
MH  - Phosphatidylinositol 3-Kinases/metabolism/*physiology
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - *Protein Biosynthesis
MH  - Vero Cells
MH  - Vesiculovirus/drug effects
EDAT- 2011/03/25 06:00
MHDA- 2011/08/06 06:00
CRDT- 2011/03/25 06:00
PHST- 2010/06/18 00:00 [received]
PHST- 2011/01/21 00:00 [accepted]
PHST- 2011/03/25 06:00 [entrez]
PHST- 2011/03/25 06:00 [pubmed]
PHST- 2011/08/06 06:00 [medline]
AID - 000324536 [pii]
AID - 10.1159/000324536 [doi]
PST - ppublish
SO  - Pharmacology. 2011;87(3-4):224-31. doi: 10.1159/000324536. Epub 2011 Mar 25.