This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
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 Cameron, J. E.
Right arrow Articles by Flemington, E. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cameron, J. E.
Right arrow Articles by Flemington, E. K.

 Previous Article  |  Next Article 

Journal of Virology, February 2008, p. 1946-1958, Vol. 82, No. 4
0022-538X/08/$08.00+0     doi:10.1128/JVI.02136-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Epstein-Barr Virus Latent Membrane Protein 1 Induces Cellular MicroRNA miR-146a, a Modulator of Lymphocyte Signaling Pathways{triangledown} ,{dagger}

Jennifer E. Cameron,1,2 Qinyan Yin,1,2,3 Claire Fewell,3 Michelle Lacey,4 Jane McBride,3 Xia Wang,3 Zhen Lin,3 Brian C. Schaefer,5 and Erik K. Flemington1,2,3*

Louisiana Cancer Research Consortium,1 Tulane Cancer Center,2 Department of Pathology,3 Department of Mathematics, Tulane University, New Orleans, Louisiana,4 Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences Center, Bethesda, Maryland5

Received 27 September 2007/ Accepted 20 November 2007

The Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) is a functional homologue of the tumor necrosis factor receptor family and contributes substantially to the oncogenic potential of EBV through activation of nuclear factor {kappa}B (NF-{kappa}B). MicroRNAs (miRNAs) are a class of small RNA molecules that are involved in the regulation of cellular processes such as growth, development, and apoptosis and have recently been linked to cancer phenotypes. Through miRNA microarray analysis, we demonstrate that LMP1 dysregulates the expression of several cellular miRNAs, including the most highly regulated of these, miR-146a. Quantitative reverse transcription-PCR analysis confirmed induced expression of miR-146a by LMP1. Analysis of miR-146a expression in EBV latency type III and type I cell lines revealed substantial expression of miR-146a in type III (which express LMP1) but not in type I cell lines. Reporter studies demonstrated that LMP1 induces miR-146a predominantly through two NF-{kappa}B binding sites in the miR-146a promoter and identified a role for an Oct-1 site in conferring basal and induced expression. Array analysis of cellular mRNAs expressed in Akata cells transduced with an miR-146a-expressing retrovirus identified genes that are directly or indirectly regulated by miR-146a, including a group of interferon-responsive genes that are inhibited by miR-146a. Since miR-146a is known to be induced by agents that activate the interferon response pathway (including LMP1), these results suggest that miR-146a functions in a negative feedback loop to modulate the intensity and/or duration of the interferon response.

* Corresponding author. Mailing address: Tulane University Health Sciences Center, 1430 Tulane Ave., SL79, New Orleans, LA 70112. Phone: (504) 988-1167. Fax: (504) 988-5516. E-mail: eflemin{at}tulane.edu

{triangledown} Published ahead of print on 5 December 2007.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, February 2008, p. 1946-1958, Vol. 82, No. 4
0022-538X/08/$08.00+0     doi:10.1128/JVI.02136-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Visone, R., Rassenti, L. Z., Veronese, A., Taccioli, C., Costinean, S., Aguda, B. D., Volinia, S., Ferracin, M., Palatini, J., Balatti, V., Alder, H., Negrini, M., Kipps, T. J., Croce, C. M. (2009). Karyotype-specific microRNA signature in chronic lymphocytic leukemia. Blood 114: 3872-3879 [Abstract] [Full Text]  
  • Hou, J., Wang, P., Lin, L., Liu, X., Ma, F., An, H., Wang, Z., Cao, X. (2009). MicroRNA-146a Feedback Inhibits RIG-I-Dependent Type I IFN Production in Macrophages by Targeting TRAF6, IRAK1, and IRAK2. J. Immunol. 183: 2150-2158 [Abstract] [Full Text]  
  • Cosmopoulos, K., Pegtel, M., Hawkins, J., Moffett, H., Novina, C., Middeldorp, J., Thorley-Lawson, D. A. (2009). Comprehensive Profiling of Epstein-Barr Virus MicroRNAs in Nasopharyngeal Carcinoma. J. Virol. 83: 2357-2367 [Abstract] [Full Text]  
  • Jazdzewski, K., Liyanarachchi, S., Swierniak, M., Pachucki, J., Ringel, M. D., Jarzab, B., de la Chapelle, A. (2009). Polymorphic mature microRNAs from passenger strand of pre-miR-146a contribute to thyroid cancer. Proc. Natl. Acad. Sci. USA 106: 1502-1505 [Abstract] [Full Text]  
  • Nana-Sinkam, S. P., Hunter, M. G., Nuovo, G. J., Schmittgen, T. D., Gelinas, R., Galas, D., Marsh, C. B. (2009). Integrating the MicroRNome into the Study of Lung Disease. Am. J. Respir. Crit. Care Med. 179: 4-10 [Abstract] [Full Text]  
  • Sheedy, F J, O'Neill, L A J (2008). Adding fuel to fire: microRNAs as a new class of mediators of inflammation. Ann Rheum Dis 67: iii50-iii55 [Abstract] [Full Text]  
  • Gatto, G., Rossi, A., Rossi, D., Kroening, S., Bonatti, S., Mallardo, M. (2008). Epstein-Barr virus latent membrane protein 1 trans-activates miR-155 transcription through the NF-{kappa}B pathway. Nucleic Acids Res 36: 6608-6619 [Abstract] [Full Text]  
  • Lovis, P., Roggli, E., Laybutt, D. R., Gattesco, S., Yang, J.-Y., Widmann, C., Abderrahmani, A., Regazzi, R. (2008). Alterations in MicroRNA Expression Contribute to Fatty Acid-Induced Pancreatic {beta}-Cell Dysfunction. Diabetes 57: 2728-2736 [Abstract] [Full Text]  
  • Schwegmann, A., Brombacher, F. (2008). Host-Directed Drug Targeting of Factors Hijacked by Pathogens. Sci Signal 1: re8-re8 [Abstract] [Full Text]  
  • Yin, Q., McBride, J., Fewell, C., Lacey, M., Wang, X., Lin, Z., Cameron, J., Flemington, E. K. (2008). MicroRNA-155 Is an Epstein-Barr Virus-Induced Gene That Modulates Epstein-Barr Virus-Regulated Gene Expression Pathways. J. Virol. 82: 5295-5306 [Abstract] [Full Text]  
  • Jazdzewski, K., Murray, E. L., Franssila, K., Jarzab, B., Schoenberg, D. R., de la Chapelle, A. (2008). Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma. Proc. Natl. Acad. Sci. USA 105: 7269-7274 [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»