Foot-and-mouth disease virus leader proteinase inhibits dsRNA-induced RANTES transcription in PK-15 cells
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Abstract
The chemokine RANTES (regulated upon activation, normal T-cells expressed and secreted) plays an essential role in inflammation and immune response. Infection with wild-type foot-and-mouth disease virus (FMDV) in PK-15 cells strongly inhibits the expression of RANTES compared to infection with a genetically engineered mutant lacking the leader protein (Lpro) coding region. This suggests that Lpro is involved in RANTES regulation. However, the underlying molecular mechanism remains unclear. In this study, we show that transfection of PK-15 cells with a plasmid expressing the Lpro of FMDV, in the absence of other FMDV proteins, inhibited dsRNA-induced RANTES transcription and promoter activity. Promoter mutagenesis experiments revealed that the interferon-stimulated response element (ISRE) was important for the ability of Lpro to inhibit dsRNA-induced RANTES promoter activity. Furthermore, over-expression of Lpro also inhibited IRF-3/7-mediated RANTES activation. Screening Lpro mutants indicated that catalytic activity and a SAP (for SAF-A/B, Acinus, and PIAS) domain of Lpro were required to suppress dsRNA-induced RANTES transcription.
Keywords
FMDV Leader proteinase RANTES Inhibition Signaling pathwayNotes
Acknowledgments
We thank Dr. Kone Yedamignou Alexis for critical review of the manuscript. This study was supported by the Program for the New Century Excellent Talent Project (NCET-07-0347) and Changjiang Scholars and Innovative Research Team in Chinese University (IRT0726).
References
- 1.M.J. Grubman, B. Baxt, Clin. Microbiol. Rev. 17, 465–493 (2004)PubMedCrossRefGoogle Scholar
- 2.P.W. Mason, M.J. Grubman, B. Baxt, Virus Res. 91, 9–32 (2003)PubMedCrossRefGoogle Scholar
- 3.W.T. Golde, C.K. Nfon, F.N. Toka, Immunol. Rev. 225, 85–95 (2008)PubMedCrossRefGoogle Scholar
- 4.M. Medina, E. Domingo, J.K. Brangwyn, G.J. Belsham, Virology 194, 355–359 (1993)PubMedCrossRefGoogle Scholar
- 5.B.E. Clarke, D.V. Sangar, J.N. Burroughs, S.E. Newton, A.R. Carroll, D.J. Rowlands, J. Gen. Virol. 66(Pt 12), 2615–2626 (1985)PubMedCrossRefGoogle Scholar
- 6.M.E. Piccone, M. Zellner, T.F. Kumosinski, P.W. Mason, M.J. Grubman, J. Virol. 69, 4950–4956 (1995)PubMedGoogle Scholar
- 7.P.J. Roberts, G.J. Belsham, Virology 213, 140–146 (1995)PubMedCrossRefGoogle Scholar
- 8.R. Kirchweger, E. Ziegler, B.J. Lamphear, D. Waters, H.D. Liebig, W. Sommergruber, F. Sobrino, C. Hohenadl, D. Blaas, R.E. Rhoads, T. Skern, J. Virol. 68, 5677–5684 (1994)PubMedGoogle Scholar
- 9.M.A. Devaney, V.N. Vakharia, R.E. Lloyd, E. Ehrenfeld, M.J. Grubman, J. Virol. 62, 4407–4409 (1988)PubMedGoogle Scholar
- 10.S. Koyama, K.J. Ishii, C. Coban, S. Akira, Cytokine 43, 336–341 (2008)PubMedCrossRefGoogle Scholar
- 11.A. Ruggieri, M. Franco, I. Gatto, A. Kumar, M. Rapicetta, BMC Gastroenterol. 7, 21 (2007)PubMedCrossRefGoogle Scholar
- 12.V. Nardese, R. Longhi, S. Polo, F. Sironi, C. Arcelloni, R. Paroni, C. DeSantis, P. Sarmientos, M. Rizzi, M. Bolognesi, V. Pavone, P. Lusso, Nat. Struct. Biol. 8, 611–615 (2001)PubMedCrossRefGoogle Scholar
- 13.M.B. Elliott, P.W. Tebbey, K.S. Pryharski, C.A. Scheuer, T.S. Laughlin, G.E. Hancock, J. Med. Virol. 73, 300–308 (2004)PubMedCrossRefGoogle Scholar
- 14.T. De Los Santos, F. Diaz-San Segundo, M.J. Grubman, J. Virol. 81, 12803–12815 (2007)CrossRefGoogle Scholar
- 15.D. Wang, L. Fang, P. Li, Q. Chen, R. Luo, H. Chen, S. Xiao, Dev. Comp. Immunol. 35, 345–351 (2011)PubMedCrossRefGoogle Scholar
- 16.D. Wang, L. Fang, R. Luo, R. Ye, Y. Fang, L. Xie, H. Chen, S. Xiao, Biochem. Biophys. Res. Commun. 399, 72–78 (2010)PubMedCrossRefGoogle Scholar
- 17.A. Casola, R.P. Garofalo, H. Haeberle, T.F. Elliott, R. Lin, M. Jamaluddin, A.R. Brasier, J. Virol. 75, 6428–6439 (2001)PubMedCrossRefGoogle Scholar
- 18.A. Casola, A. Henderson, T. Liu, R.P. Garofalo, A.R. Brasier, Am. J. Physiol. Lung Cell. Mol. Physiol. 283, L1280–L1290 (2002)PubMedGoogle Scholar
- 19.P. Genin, M. Algarte, P. Roof, R. Lin, J. Hiscott, J. Immunol. 164, 5352–5361 (2000)PubMedGoogle Scholar
- 20.J. Melchjorsen, S.R. Paludan, J. Gen. Virol. 84, 2491–2495 (2003)PubMedCrossRefGoogle Scholar
- 21.R. Lin, R.S. Noyce, S.E. Collins, R.D. Everett, K.L. Mossman, J. Virol. 78, 1675–1684 (2004)PubMedCrossRefGoogle Scholar
- 22.S. Lefort, A. Soucy-Faulkner, N. Grandvaux, L. Flamand, J. Virol. 81, 10950–10960 (2007)PubMedCrossRefGoogle Scholar
- 23.R. Lin, P. Genin, Y. Mamane, M. Sgarbanti, A. Battistini, W.J. Harrington Jr., G.N. Barber, J. Hiscott, Oncogene 20, 800–811 (2001)PubMedCrossRefGoogle Scholar
- 24.N. Foeger, W. Glaser, T. Skern, J. Biol. Chem. 277, 44300–44309 (2002)PubMedCrossRefGoogle Scholar
- 25.P. Schlick, J. Kronovetr, B. Hampoelz, T. Skern, Biochem. J. 363, 493–501 (2002)PubMedCrossRefGoogle Scholar
- 26.T. de los Santos, F.D. Segundo, J. Zhu, M. Koster, C.C. Dias, M.J. Grubman, J. Virol. 83, 1800–1810 (2009)PubMedCrossRefGoogle Scholar