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

被引:67
作者
Seo, Young-Jin [1 ,2 ]
Pritzl, Curtis J. [1 ,2 ]
Vijayan, Madhuvanthi [1 ,2 ]
Bomb, Kavita [1 ,2 ]
McClain, Mariah E. [1 ,2 ]
Alexander, Stephen [3 ]
Hahm, Bumsuk [1 ,2 ]
机构
[1] Univ Missouri, Dept Surg & Mol Microbiol, Columbia, MO 65211 USA
[2] Univ Missouri, Dept Immunol, Columbia, MO USA
[3] Univ Missouri, Div Biol Sci, Columbia, MO 65211 USA
来源
PLOS ONE | 2013年 / 8卷 / 08期
关键词
NF-KAPPA-B; RAN-BINDING PROTEIN-3; MATRIX PROTEIN; A VIRUSES; ACTIVATION; INHIBITION; PROPAGATION; 1-PHOSPHATE; INDUCTION; TARGET;
D O I
10.1371/journal.pone.0075005
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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-kappa B 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.
引用
收藏
页数:13
相关论文
共 70 条
[1]   Sphingosine-1-phosphate is a missing cofactor for the E3 ubiquitin ligase TRAF2 [J].
Alvarez, Sergio E. ;
Harikumar, Kuzhuvelil B. ;
Hait, Nitai C. ;
Allegood, Jeremy ;
Strub, Graham M. ;
Kim, Eugene Y. ;
Maceyka, Michael ;
Jiang, Hualiang ;
Luo, Cheng ;
Kordula, Tomasz ;
Milstien, Sheldon ;
Spiegel, Sarah .
NATURE, 2010, 465 (7301) :1084-U149
[2]  
[Anonymous], 2011, Wkly Epidemiol Rec, V86, P497
[3]   Influenza virus hemagglutinin stimulates the protein kinase C activity of human polymorphonuclear leucocytes [J].
Arora, DJS ;
Gasse, N .
ARCHIVES OF VIROLOGY, 1998, 143 (10) :2029-2037
[4]   Role of the influenza virus M1 protein in nuclear export of viral ribonucleoproteins [J].
Bui, M ;
Wills, EG ;
Helenius, A ;
Whittaker, GR .
JOURNAL OF VIROLOGY, 2000, 74 (04) :1781-1786
[5]   Sphingosine kinase 1 in viral infections [J].
Carr, Jillian M. ;
Mahalingam, Suresh ;
Bonder, Claudine S. ;
Pitson, Stuart M. .
REVIEWS IN MEDICAL VIROLOGY, 2013, 23 (02) :73-84
[6]   Nuclear Export of Smad2 and Smad3 by RanBP3 Facilitates Termination of TGF-β Signaling [J].
Dai, Fangyan ;
Lin, Xia ;
Chang, Chenbei ;
Feng, Xin-Hua .
DEVELOPMENTAL CELL, 2009, 16 (03) :345-357
[7]   N,N-dimethylsphingosine is a potent competitive inhibitor of sphingosine kinase but not of protein kinase C:: Modulation of cellular levels of sphingosine 1-phosphate and ceramide [J].
Edsall, LC ;
Van Brocklyn, JR ;
Cuvillier, O ;
Kleuser, B ;
Spiegel, S .
BIOCHEMISTRY, 1998, 37 (37) :12892-12898
[8]   Bivalent role of the phosphatidylinositol-3-kinase (PI3K) during influenza virus infection and host cell defence [J].
Ehrhardt, Christina ;
Marjuki, Henju ;
Wolff, Thorsten ;
Nuernberg, Bernd ;
Planz, Oliver ;
Pleschka, Stephan ;
Ludwig, Stephan .
CELLULAR MICROBIOLOGY, 2006, 8 (08) :1336-1348
[9]   The influenza A virus matrix protein as a marker to monitor initial virus internalisation [J].
Eierhoff, Thorsten ;
Ludwig, Stephan ;
Ehrhardt, Christina .
BIOLOGICAL CHEMISTRY, 2009, 390 (5-6) :509-515
[10]   Interaction of the influenza virus nucleoprotein with the cellular CRM1-mediated nuclear export pathway [J].
Elton, D ;
Simpson-Holley, M ;
Archer, K ;
Medcalf, L ;
Hallam, R ;
McCauley, J ;
Digard, P .
JOURNAL OF VIROLOGY, 2001, 75 (01) :408-419