Published ahead of print on January 23, 2004, doi:10.1165/rcmb.2003-0424OC
Am. J. Respir. Cell Mol. Biol., Volume 30, Number 6, June 2004, 844-852
A more recent version of this article appeared on June 1, 2004
Submitted on November 24, 2003
Revised on January 23, 2004
Sphingosine Kinase Mediates Activation of ERK and Akt by Respiratory Syncytial Virus
Martha M Monick1*, Kelli Cameron1, Linda S Powers1, Noah S Butler1, Diann McCoy1, Rama K Mallampalli1, and Gary W Hunninghake1
1 Internal Medicine, University of Iowa, Iowa City, Iowa, USA
* To whom correspondence should be addressed. E-mail: martha-monick{at}uiowa.edu.
Respiratory syncytial virus (RSV) preferentially infects lung epithelial cells. Infected cells remain viable well into the infection. This prolonged survival results from RSV-induced activation of pro-survival pathways, including Akt and extracellular signal-related kinase (ERK). Sphingosine 1-phosphate (S1P) is a sphingolipid metabolite with demonstrated links to cell survival. It is enzymatically generated by sequential activation of ceramidase (generation of sphingosine) and sphingosine kinase (generation of S1P). In these studies, we found that RSV stimulated neutral ceramidase and sphingosine kinase activities in lung epithelial cells. The combined effect of activation of these two enzymes would decrease pro-apoptotic ceramide and increase anti-apoptotic S1P. S1P activated Akt and ERK within minutes and inhibition of sphingosine kinase blocked RSV-induced ERK and Akt activation leading to accelerated cell death after viral infection. RSV infection does eventually kill infected cells but activation of cell survival pathways significantly delays cell death. The studies are the first evidence linking sphingolipid metabolites to cell survival mechanisms in the context of a viral infection.
This article has been cited by other articles:
|
|
|
|
 
M. M. Monick, L. S. Powers, I. Hassan, D. Groskreutz, T. O. Yarovinsky, C. W. Barrett, E. M. Castilow, D. Tifrea, S. M. Varga, and G. W. Hunninghake
Respiratory Syncytial Virus Synergizes with Th2 Cytokines to Induce Optimal Levels of TARC/CCL17
J. Immunol.,
August 1, 2007;
179(3):
1648 - 1658.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. J. Kim, Y. Lee, E.-J. Chang, H.-M. Kim, S.-P. Hong, Z. H. Lee, J. Ryu, and H.-H. Kim
Suppression of Osteoclastogenesis by N,N-Dimethyl-D-erythro-sphingosine: A Sphingosine Kinase Inhibition-Independent Action
Mol. Pharmacol.,
August 1, 2007;
72(2):
418 - 428.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Bitko, O. Shulyayeva, B. Mazumder, A. Musiyenko, M. Ramaswamy, D. C. Look, and S. Barik
Nonstructural Proteins of Respiratory Syncytial Virus Suppress Premature Apoptosis by an NF-{kappa}B-Dependent, Interferon-Independent Mechanism and Facilitate Virus Growth
J. Virol.,
February 15, 2007;
81(4):
1786 - 1795.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Yadav, L. Clark, and J. S. Schorey
Macrophage's Proinflammatory Response to a Mycobacterial Infection Is Dependent on Sphingosine Kinase-Mediated Activation of Phosphatidylinositol Phospholipase C, Protein Kinase C, ERK1/2, and Phosphatidylinositol 3-Kinase
J. Immunol.,
May 1, 2006;
176(9):
5494 - 5503.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. W. McL. Rixon, G. Brown, J. T. Murray, and R. J. Sugrue
The respiratory syncytial virus small hydrophobic protein is phosphorylated via a mitogen-activated protein kinase p38-dependent tyrosine kinase activity during virus infection
J. Gen. Virol.,
February 1, 2005;
86(2):
375 - 384.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. V. Truong, M. M. Monick, T. O. Yarovinsky, L. S. Powers, T. Nyunoya, and G. W. Hunninghake
Extracellular Signal-Regulated Kinase Activation Delays Hyperoxia-Induced Epithelial Cell Death in Conditions of Akt Downregulation
Am. J. Respir. Cell Mol. Biol.,
December 1, 2004;
31(6):
611 - 618.
[Abstract]
[Full Text]
[PDF]
|
|
|
Copyright © 2004 American Thoracic Society.
|
|
|
