tetano
Editor, Senior Moderator
PLoS One. 2013 Aug 30;8(8):e75005. doi: 10.1371/journal.pone.0075005.
Sphingosine Kinase 1 Serves as a Pro-Viral Factor by Regulating Viral RNA Synthesis and Nuclear Export of Viral Ribonucleoprotein Complex upon Influenza Virus Infection.
Seo YJ, Pritzl CJ, Vijayan M, Bomb K, McClain ME, Alexander S, Hahm B.
Source
Departments of Surgery & Molecular Microbiology and Immunology, University of Missouri-Columbia, Columbia, Missouri, United States of America.
Abstract
Influenza continues to pose a threat to humans by causing significant morbidity and mortality. Thus, it is imperative to investigate mechanisms by which influenza virus manipulates the function of host factors and cellular signal pathways. In this study, we demonstrate that influenza virus increases the expression and activation of sphingosine kinase (SK) 1, which in turn regulates diverse cellular signaling pathways. Inhibition of SK suppressed virus-induced NF-κB activation and markedly reduced the synthesis of viral RNAs and proteins. Further, SK blockade interfered with activation of Ran-binding protein 3 (RanBP3), a cofactor of chromosome region maintenance 1 (CRM1), to inhibit CRM1-mediated nuclear export of the influenza viral ribonucleoprotein complex. In support of this observation, SK inhibition altered the phosphorylation of ERK, p90RSK, and AKT, which is the upstream signal of RanBP3/CRM1 activation. Collectively, these results indicate that SK is a key pro-viral factor regulating multiple cellular signal pathways triggered by influenza virus infection.
PMID:
24137500
[PubMed - in process]
PMCID:
PMC3796690
Free PMC Article
http://www.ncbi.nlm.nih.gov/pubmed/24137500
Sphingosine Kinase 1 Serves as a Pro-Viral Factor by Regulating Viral RNA Synthesis and Nuclear Export of Viral Ribonucleoprotein Complex upon Influenza Virus Infection.
Seo YJ, Pritzl CJ, Vijayan M, Bomb K, McClain ME, Alexander S, Hahm B.
Source
Departments of Surgery & Molecular Microbiology and Immunology, University of Missouri-Columbia, Columbia, Missouri, United States of America.
Abstract
Influenza continues to pose a threat to humans by causing significant morbidity and mortality. Thus, it is imperative to investigate mechanisms by which influenza virus manipulates the function of host factors and cellular signal pathways. In this study, we demonstrate that influenza virus increases the expression and activation of sphingosine kinase (SK) 1, which in turn regulates diverse cellular signaling pathways. Inhibition of SK suppressed virus-induced NF-κB activation and markedly reduced the synthesis of viral RNAs and proteins. Further, SK blockade interfered with activation of Ran-binding protein 3 (RanBP3), a cofactor of chromosome region maintenance 1 (CRM1), to inhibit CRM1-mediated nuclear export of the influenza viral ribonucleoprotein complex. In support of this observation, SK inhibition altered the phosphorylation of ERK, p90RSK, and AKT, which is the upstream signal of RanBP3/CRM1 activation. Collectively, these results indicate that SK is a key pro-viral factor regulating multiple cellular signal pathways triggered by influenza virus infection.
PMID:
24137500
[PubMed - in process]
PMCID:
PMC3796690
Free PMC Article
http://www.ncbi.nlm.nih.gov/pubmed/24137500