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 Liang, X.
Right arrow Articles by Jung, J. U.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Liang, X.
Right arrow Articles by Jung, J. U.

 Previous Article  |  Next Article 

Journal of Virology, November 2004, p. 12416-12427, Vol. 78, No. 22
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.22.12416-12427.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Inhibition of Interferon-Mediated Antiviral Activity by Murine Gammaherpesvirus 68 Latency-Associated M2 Protein

Xiaozhen Liang, Young C. Shin, Robert E. Means, and Jae U. Jung*

Department of Microbiology and Molecular Genetics and Tumor Virology Division, New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts

Received 15 April 2004/ Accepted 29 June 2004

Upon viral infection, the major defense mounted by the host immune system is the activation of the interferon (IFN)-mediated antiviral pathway. In order to complete their life cycle, viruses that are obligatory intracellular parasites must modulate the host IFN-mediated immune response. Murine gammaherpesvirus 68 ({gamma}HV68) infects a wide range of cell types and establishes latent infections in mice. Here we demonstrate that the {gamma}HV68 latency-associated M2 protein has a cell-type-dependent localization pattern: M2 is present in the cytoplasm and plasma membrane in lymphocytes, whereas it is present primarily in the nucleus in epithelial and fibroblast cells. A mutational analysis indicated that the internal positively charged amino acids of M2 are required for its nuclear localization in fibroblasts. Purification of the M2 complex showed that M2 specifically interacts with the cellular p32 acidic protein through its central positively charged region and that this interaction recruits the cellular p32 protein to the nucleus in fibroblasts. Regardless of its localization, M2 expression effectively induced the downregulation of STAT1 and/or STAT2 in both A20 B lymphocytes and NIH 3T3 fibroblasts, resulting in the inhibition of IFN-{alpha}/ß- and IFN-{gamma}-mediated transcriptional activation. Finally, the M2 interaction with the p32 protein appeared to contribute to its ability to inhibit IFN-mediated transcriptional activation. These results indicate that {gamma}HV68 harbors a latency-associated M2 gene that antagonizes IFN-mediated host innate immunity and thus could play an important role in the establishment and maintenance of viral latency in infected animals.

* Corresponding author. Mailing address: New England Regional Primate Research Center, 1 Pine Hill Dr., Southborough, MA 01772. Phone: (508) 624-8083. Fax: (508) 786-1416. E-mail: jae_jung{at}hms.harvard.edu.

Journal of Virology, November 2004, p. 12416-12427, Vol. 78, No. 22
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.22.12416-12427.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Le, V. T. K., Trilling, M., Wilborn, M., Hengel, H., Zimmermann, A. (2008). Human cytomegalovirus interferes with signal transducer and activator of transcription (STAT) 2 protein stability and tyrosine phosphorylation. J. Gen. Virol. 89: 2416-2426 [Abstract] [Full Text]  
  • DeZalia, M., Speck, S. H. (2008). Identification of Closely Spaced but Distinct Transcription Initiation Sites for the Murine Gammaherpesvirus 68 Latency-Associated M2 Gene. J. Virol. 82: 7411-7421 [Abstract] [Full Text]  
  • Forrest, J. C., Speck, S. H. (2008). Establishment of B-Cell Lines Latently Infected with Reactivation-Competent Murine Gammaherpesvirus 68 Provides Evidence for Viral Alteration of a DNA Damage-Signaling Cascade. J. Virol. 82: 7688-7699 [Abstract] [Full Text]  
  • Herskowitz, J. H., Siegel, A. M., Jacoby, M. A., Speck, S. H. (2008). Systematic Mutagenesis of the Murine Gammaherpesvirus 68 M2 Protein Identifies Domains Important for Chronic Infection. J. Virol. 82: 3295-3310 [Abstract] [Full Text]  
  • Weslow-Schmidt, J. L., Jewell, N. A., Mertz, S. E., Simas, J. P., Durbin, J. E., Flano, E. (2007). Type I Interferon Inhibition and Dendritic Cell Activation during Gammaherpesvirus Respiratory Infection. J. Virol. 81: 9778-9789 [Abstract] [Full Text]  
  • Mora, A. L., Torres-Gonzalez, E., Rojas, M., Xu, J., Ritzenthaler, J., Speck, S. H., Roman, J., Brigham, K., Stecenko, A. (2007). Control of Virus Reactivation Arrests Pulmonary Herpesvirus-induced Fibrosis in IFN-{gamma} Receptor-deficient Mice. Am. J. Respir. Crit. Care Med. 175: 1139-1150 [Abstract] [Full Text]  
  • Liang, X., Pickering, M. T., Cho, N.-H., Chang, H., Volkert, M. R., Kowalik, T. F., Jung, J. U. (2006). Deregulation of DNA Damage Signal Transduction by Herpesvirus Latency-Associated M2.. J. Virol. 80: 5862-5874 [Abstract] [Full Text]  
  • Rodrigues, L., Pires de Miranda, M., Caloca, M. J., Bustelo, X. R., Simas, J. P. (2006). Activation of Vav by the Gammaherpesvirus M2 Protein Contributes to the Establishment of Viral Latency in B Lymphocytes.. J. Virol. 80: 6123-6135 [Abstract] [Full Text]  
  • Ohrmalm, C., Akusjarvi, G. (2006). Cellular Splicing and Transcription Regulatory Protein p32 Represses Adenovirus Major Late Transcription and Causes Hyperphosphorylation of RNA Polymerase II.. J. Virol. 80: 5010-5020 [Abstract] [Full Text]  
  • Barton, E. S., Lutzke, M. L., Rochford, R., Virgin, H. W. IV (2005). Alpha/Beta Interferons Regulate Murine Gammaherpesvirus Latent Gene Expression and Reactivation from Latency. J. Virol. 79: 14149-14160 [Abstract] [Full Text]  
  • Waggoner, S. N., Cruise, M. W., Kassel, R., Hahn, Y. S. (2005). gC1q Receptor Ligation Selectively Down-Regulates Human IL-12 Production through Activation of the Phosphoinositide 3-Kinase Pathway. J. Immunol. 175: 4706-4714 [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»