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 Le Roy, E.
Right arrow Articles by Davignon, J.-L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Le Roy, E.
Right arrow Articles by Davignon, J.-L.

 Previous Article  |  Next Article 

Journal of Virology, August 1999, p. 6582-6589, Vol. 73, No. 8
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Escape of Human Cytomegalovirus from HLA-DR-Restricted CD4+ T-Cell Response Is Mediated by Repression of Gamma Interferon-Induced Class II Transactivator Expressiondagger

Emmanuelle Le Roy,1 Annick Mühlethaler-Mottet,2 Christian Davrinche,1 Bernard Mach,2 and Jean-Luc Davignon1,*

INSERM U 395, Toulouse, France,1 and Louis Jeantet Laboratory of Molecular Genetics, Department of Genetics and Microbiology, University of Geneva Medical School, Geneva, Switzerland2

Received 1 March 1999/Accepted 14 May 1999

Human cytomegalovirus (HCMV), a betaherpesvirus, is a pathogen which escapes immune recognition through various mechanisms. In this paper, we show that HCMV down regulates gamma interferon (IFN-gamma )-induced HLA-DR expression in U373 MG astrocytoma cells due to a defect downstream of STAT1 phosphorylation and nuclear translocation. Repression of class II transactivator (CIITA) mRNA expression is detected within the first hours of IFN-gamma -HCMV coincubation and results in the absence of HLA-DR synthesis. This defect leads to the absence of presentation of the major immediate-early protein IE1 to specific CD4+ T-cell clones when U373 MG cells, used as antigen-presenting cells, are treated with IFN-gamma plus HCMV. However, presentation of endogenously synthesized IE1 can be restored when U373 MG cells are transfected with CIITA prior to infection with HCMV. Altogether, the data indicate that the defect induced by HCMV resides in the activation of the IFN-gamma -responsive promoter of CIITA. This is the first demonstration of a viral inhibition of CIITA expression.

* Corresponding author. Mailing address: INSERM U 395, CHU Purpan, BP 3028, 31024 Toulouse Cedex, France. Phone: 33 5 62 74 83 76. Fax: 33 5 62 74 83 86. E-mail: davignon{at}purpan.inserm.fr.

dagger This work is dedicated to the memory of our friend and colleague Claude de Préval.

Journal of Virology, August 1999, p. 6582-6589, Vol. 73, No. 8
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Baron, M., Davignon, J.-L. (2008). Inhibition of IFN-{gamma}-Induced STAT1 Tyrosine Phosphorylation by Human CMV Is Mediated by SHP2. J. Immunol. 181: 5530-5536 [Abstract] [Full Text]  
  • 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]  
  • Hussain, A., Wesley, C., Khalid, M., Chaudhry, A., Jameel, S. (2008). Human Immunodeficiency Virus Type 1 Vpu Protein Interacts with CD74 and Modulates Major Histocompatibility Complex Class II Presentation. J. Virol. 82: 893-902 [Abstract] [Full Text]  
  • Delmas, S., Brousset, P., Clement, D., Le Roy, E., Davignon, J.-L. (2007). Anti-IE1 CD4+ T-cell clones kill peptide-pulsed, but not human cytomegalovirus-infected, target cells. J. Gen. Virol. 88: 2441-2449 [Abstract] [Full Text]  
  • Wiertz, E. J., Devlin, R., Collins, H. L., Ressing, M. E. (2007). Herpesvirus Interference with Major Histocompatibility Complex Class II-Restricted T-Cell Activation. J. Virol. 81: 4389-4396 [Full Text]  
  • Popkin, D. L., Watson, M. A., Karaskov, E., Dunn, G. P., Bremner, R., Virgin, H. W. IV (2003). Murine cytomegalovirus paralyzes macrophages by blocking IFN{gamma}-induced promoter assembly. Proc. Natl. Acad. Sci. USA 100: 14309-14314 [Abstract] [Full Text]  
  • Hegde, N. R., Johnson, D. C. (2003). Human Cytomegalovirus US2 Causes Similar Effects on Both Major Histocompatibility Complex Class I and II Proteins in Epithelial and Glial Cells. J. Virol. 77: 9287-9294 [Abstract] [Full Text]  
  • Odeberg, J., Plachter, B., Branden, L., Soderberg-Naucler, C. (2003). Human cytomegalovirus protein pp65 mediates accumulation of HLA-DR in lysosomes and destruction of the HLA-DR {alpha}-chain. Blood 101: 4870-4877 [Abstract] [Full Text]  
  • Odeberg, J., Browne, H., Metkar, S., Froelich, C. J., Branden, L., Cosman, D., Soderberg-Naucler, C. (2003). The Human Cytomegalovirus Protein UL16 Mediates Increased Resistance to Natural Killer Cell Cytotoxicity through Resistance to Cytolytic Proteins. J. Virol. 77: 4539-4545 [Abstract] [Full Text]  
  • Ilangumaran, S., Finan, D., La Rose, J., Raine, J., Silverstein, A., De Sepulveda, P., Rottapel, R. (2002). A Positive Regulatory Role for Suppressor of Cytokine Signaling 1 in IFN-{gamma}-Induced MHC Class II Expression in Fibroblasts. J. Immunol. 169: 5010-5020 [Abstract] [Full Text]  
  • Hegde, N. R., Tomazin, R. A., Wisner, T. W., Dunn, C., Boname, J. M., Lewinsohn, D. M., Johnson, D. C. (2002). Inhibition of HLA-DR Assembly, Transport, and Loading by Human Cytomegalovirus Glycoprotein US3: a Novel Mechanism for Evading Major Histocompatibility Complex Class II Antigen Presentation. J. Virol. 76: 10929-10941 [Abstract] [Full Text]  
  • Slobedman, B., Mocarski, E. S., Arvin, A. M., Mellins, E. D., Abendroth, A. (2002). Latent cytomegalovirus down-regulates major histocompatibility complex class II expression on myeloid progenitors. Blood 100: 2867-2873 [Abstract] [Full Text]  
  • Le Roy, E., Baron, M., Faigle, W., Clement, D., Lewinsohn, D. M., Streblow, D. N., Nelson, J. A., Amigorena, S., Davignon, J.-L. (2002). Infection of APC by Human Cytomegalovirus Controlled Through Recognition of Endogenous Nuclear Immediate Early Protein 1 by Specific CD4+ T Lymphocytes. J. Immunol. 169: 1293-1301 [Abstract] [Full Text]  
  • Vaz-Santiago, J., Lule, J., Rohrlich, P., Jacquier, C., Gibert, N., Le Roy, E., Betbeder, D., Davignon, J.-L., Davrinche, C. (2001). Ex Vivo Stimulation and Expansion of both CD4+ and CD8+ T Cells from Peripheral Blood Mononuclear Cells of Human Cytomegalovirus-Seropositive Blood Donors by Using a Soluble Recombinant Chimeric Protein, IE1-pp65. J. Virol. 75: 7840-7847 [Abstract] [Full Text]  
  • Odeberg, J., Söderberg-Nauclér, C. (2001). Reduced Expression of HLA Class II Molecules and Interleukin-10- and Transforming Growth Factor {beta}1-Independent Suppression of T-Cell Proliferation in Human Cytomegalovirus-Infected Macrophage Cultures. J. Virol. 75: 5174-5181 [Abstract] [Full Text]  
  • Presti, R. M., Popkin, D. L., Connick, M., Paetzold, S., Virgin, H. W. IV (2001). Novel Cell Type-Specific Antiviral Mechanism of Interferon {gamma} Action in Macrophages. JEM 193: 483-496 [Abstract] [Full Text]  
  • Gao, J., De, B. P., Han, Y., Choudhary, S., Ransohoff, R., Banerjee, A. K. (2001). Human Parainfluenza Virus Type 3 Inhibits Gamma Interferon-Induced Major Histocompatibility Complex Class II Expression Directly and by Inducing Alpha/Beta Interferon. J. Virol. 75: 1124-1131 [Abstract] [Full Text]  
  • Harton, J. A., Ting, J. P.-Y. (2000). Class II Transactivator: Mastering the Art of Major Histocompatibility Complex Expression. Mol. Cell. Biol. 20: 6185-6194 [Full Text]  
  • Pancio, H. A., Vander Heyden, N., Kosuri, K., Cresswell, P., Ratner, L. (2000). Interaction of Human Immunodeficiency Virus Type 2 Vpx and Invariant Chain. J. Virol. 74: 6168-6172 [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»