This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Dong, B.
Right arrow Articles by Silverman, R. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dong, B.
Right arrow Articles by Silverman, R. H.

 Previous Article  |  Next Article 

Journal of Virology, September 2004, p. 8983-8993, Vol. 78, No. 17
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.17.8983-8993.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Phospholipid Scramblase 1 Potentiates the Antiviral Activity of Interferon

Beihua Dong,1 Quansheng Zhou,2 Ji Zhao,2 Aimin Zhou,3 Ronald N. Harty,4 Santanu Bose,5 Amiya Banerjee,5 Roger Slee,1 Jeanna Guenther,1 Bryan R. G. Williams,1 Therese Wiedmer,2 Peter J. Sims,2,{dagger} and Robert H. Silverman1,{dagger}*

The Departments of Cancer Biology,1 Molecular Biology, Lerner Research Institute, The Cleveland Clinic Foundation,5 The Department of Chemistry, Cleveland State University, Cleveland, Ohio,3 The Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California,2 The Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania4

Received 14 March 2004/ Accepted 14 April 2004

Phospholipid scramblase 1 (PLSCR1) is an interferon (IFN)- and growth factor-inducible, calcium-binding protein that either inserts into the plasma membrane or binds DNA in the nucleus depending on its state of palmyitoylation. In certain hematopoietic cells, PLSCR1 is required for normal maturation and terminal differentiation from progenitor cells as regulated by select growth factors, where it promotes recruitment and activation of Src kinases. PLSCR1 is a substrate of Src (and Abl) kinases, and transcription of the PLSCR1 gene is regulated by the same growth factor receptor pathways in which PLSCR1 potentiates afferent signaling. The marked transcriptional upregulation of PLSCR1 by IFNs led us to explore whether PLSCR1 plays an analogous role in cellular responses to IFN, with specific focus on antiviral activities. Accordingly, human cells in which PLSCR1 expression was decreased with short interfering RNA were rendered relatively insensitive to the antiviral activity of IFNs, resulting in higher titers of vesicular stomatitis virus (VSV) and encephalomyocarditis virus. Similarly, VSV replicated to higher titers in mouse PLSCR1–/– embryonic fibroblasts than in identical cells transduced to express PLSCR1. PLSCR1 inhibited accumulation of primary VSV transcripts, similar to the effects of IFN against VSV. The antiviral effect of PLSCR1 correlated with increased expression of a subset of IFN-stimulated genes (ISGs), including ISG15, ISG54, p56, and guanylate binding proteins. Our results suggest that PLSCR1, which is itself an ISG-encoded protein, provides a mechanism for amplifying and enhancing the IFN response through increased expression of a select subset of potent antiviral genes.

* Corresponding author. Mailing address: Department of Cancer Biology, NB40, The Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195. Phone: (216) 445-9650. Fax: (216) 445-6269. E-mail: silverr{at}ccf.org.

{dagger} These authors were equal contributors to this study.

Journal of Virology, September 2004, p. 8983-8993, Vol. 78, No. 17
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.17.8983-8993.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Huett, A., Ng, A., Cao, Z., Kuballa, P., Komatsu, M., Daly, M. J., Podolsky, D. K., Xavier, R. J. (2009). A Novel Hybrid Yeast-Human Network Analysis Reveals an Essential Role for FNBP1L in Antibacterial Autophagy. J. Immunol. 182: 4917-4930 [Abstract] [Full Text]  
  • Proud, D., Turner, R. B., Winther, B., Wiehler, S., Tiesman, J. P., Reichling, T. D., Juhlin, K. D., Fulmer, A. W., Ho, B. Y., Walanski, A. A., Poore, C. L., Mizoguchi, H., Jump, L., Moore, M. L., Zukowski, C. K., Clymer, J. W. (2008). Gene Expression Profiles during In Vivo Human Rhinovirus Infection: Insights into the Host Response. Am. J. Respir. Crit. Care Med. 178: 962-968 [Abstract] [Full Text]  
  • Amir-Moazami, O., Alexia, C., Charles, N., Launay, P., Monteiro, R. C., Benhamou, M. (2008). Phospholipid Scramblase 1 Modulates a Selected Set of IgE Receptor-mediated Mast Cell Responses through LAT-dependent Pathway. J. Biol. Chem. 283: 25514-25523 [Abstract] [Full Text]  
  • Bouyssie, D., de Peredo, A. G., Mouton, E., Albigot, R., Roussel, L., Ortega, N., Cayrol, C., Burlet-Schiltz, O., Girard, J.-P., Monsarrat, B. (2007). Mascot File Parsing and Quantification (MFPaQ), a New Software to Parse, Validate, and Quantify Proteomics Data Generated by ICAT and SILAC Mass Spectrometric Analyses: Application To the Proteomics Study of Membrane Proteins from Primary Human Endothelial Cells . Mol. Cell. Proteomics 6: 1621-1637 [Abstract] [Full Text]  
  • Sariol, C. A., Munoz-Jordan, J. L., Abel, K., Rosado, L. C., Pantoja, P., Giavedoni, L., Rodriguez, I. V., White, L. J., Martinez, M., Arana, T., Kraiselburd, E. N. (2007). Transcriptional Activation of Interferon-Stimulated Genes but Not of Cytokine Genes after Primary Infection of Rhesus Macaques with Dengue Virus Type 1. CVI 14: 756-766 [Abstract] [Full Text]  
  • Munoz-Fontela, C., Garcia, M. A., Collado, M., Marcos-Villar, L., Gallego, P., Esteban, M., Rivas, C. (2007). Control of virus infection by tumour suppressors. Carcinogenesis 28: 1140-1144 [Abstract] [Full Text]  
  • Drenan, R. M., Doupnik, C. A., Jayaraman, M., Buchwalter, A. L., Kaltenbronn, K. M., Huettner, J. E., Linder, M. E., Blumer, K. J. (2006). R7BP Augments the Function of RGS7{middle dot}Gbeta5 Complexes by a Plasma Membrane-targeting Mechanism. J. Biol. Chem. 281: 28222-28231 [Abstract] [Full Text]  
  • Basu, M., Maitra, R. K., Xiang, Y., Meng, X., Banerjee, A. K., Bose, S. (2006). Inhibition of vesicular stomatitis virus infection in epithelial cells by alpha interferon-induced soluble secreted proteins. J. Gen. Virol. 87: 2653-2662 [Abstract] [Full Text]  
  • Gupta, A., Williams, B. R.G., Hanash, S. M., Rawwas, J. (2006). Cellular Retinoic Acid-Binding Protein II Is a Direct Transcriptional Target of MycN in Neuroblastoma. Cancer Res. 66: 8100-8108 [Abstract] [Full Text]  
  • Acharya, U., Edwards, M. B., Jorquera, R. A., Silva, H., Nagashima, K., Labarca, P., Acharya, J. K. (2006). Drosophila melanogaster Scramblases modulate synaptic transmission.. JCB 173: 69-82 [Abstract] [Full Text]  
  • Zhao, K.-W., Li, D., Zhao, Q., Huang, Y., Silverman, R. H., Sims, P. J., Chen, G.-Q. (2005). Interferon-{alpha}-induced Expression of Phospholipid Scramblase 1 through STAT1 Requires the Sequential Activation of Protein Kinase C{delta} and JNK. J. Biol. Chem. 280: 42707-42714 [Abstract] [Full Text]  
  • Zhou, Q., Ben-Efraim, I., Bigcas, J.-L., Junqueira, D., Wiedmer, T., Sims, P. J. (2005). Phospholipid Scramblase 1 Binds to the Promoter Region of the Inositol 1,4,5-Triphosphate Receptor Type 1 Gene to Enhance Its Expression. J. Biol. Chem. 280: 35062-35068 [Abstract] [Full Text]  
  • Malathi, K., Paranjape, J. M., Bulanova, E., Shim, M., Guenther-Johnson, J. M., Faber, P. W., Eling, T. E., Williams, B. R. G., Silverman, R. H. (2005). A transcriptional signaling pathway in the IFN system mediated by 2'-5'-oligoadenylate activation of RNase L. Proc. Natl. Acad. Sci. USA 102: 14533-14538 [Abstract] [Full Text]  
  • Wiedmer, T., Zhao, J., Li, L., Zhou, Q., Hevener, A., Olefsky, J. M., Curtiss, L. K., Sims, P. J. (2004). Adiposity, dyslipidemia, and insulin resistance in mice with targeted deletion of phospholipid scramblase 3 (PLSCR3). Proc. Natl. Acad. Sci. USA 101: 13296-13301 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»