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 Holtappels, R.
Right arrow Articles by Reddehase, M. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Holtappels, R.
Right arrow Articles by Reddehase, M. J.

 Previous Article  |  Next Article 

Journal of Virology, September 1998, p. 7201-7212, Vol. 72, No. 9
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Control of Murine Cytomegalovirus in the Lungs: Relative but Not Absolute Immunodominance of the Immediate-Early 1 Nonapeptide during the Antiviral Cytolytic T-Lymphocyte Response in Pulmonary Infiltrates

Rafaela Holtappels,1 Jürgen Podlech,1 Gernot Geginat,2 Hans-Peter Steffens,1 Doris Thomas,1 and Matthias J. Reddehase1,*

Institute for Virology, Johannes Gutenberg-University, 55101 Mainz,1 and Institute for Microbiology and Hygiene, Ruprecht-Karls University Heidelberg, 68167 Mannheim,2 Germany

Received 12 March 1998/Accepted 12 June 1998

The lungs are a major organ site of cytomegalovirus (CMV) infection, pathogenesis, and latency. Interstitial CMV pneumonia represents a critical manifestation of CMV disease, in particular in recipients of bone marrow transplantation (BMT). We have employed a murine model for studying the immune response to CMV in the lungs in the specific scenario of immune reconstitution after syngeneic BMT. Control of pulmonary infection was associated with a vigorous infiltration of the lungs, which was characterized by a preferential recruitment and massive expansion of the CD8 subset of alpha /beta T cells. The infiltrate provided a microenvironment in which the CD8 T cells differentiated into mature effector cells, that is, into functionally active cytolytic T lymphocytes (CTL). This gave us the opportunity for an ex vivo testing of the antigen specificities of CTL present at a relevant organ site of viral pathogenesis. The contribution of the previously identified immediate-early 1 (IE1) nonapeptide of murine CMV was evaluated by comparison with the CD3varepsilon -redirected cytolytic activity used as a measure of the overall CTL response in the lungs. The IE1 peptide was detected by pulmonary CTL, but it accounted for a minor part of the response. Interestingly, no additional viral or virus-induced antigenic peptides were detectable among naturally processed peptides derived from infected lungs, even though infected fibroblasts were recognized in a major histocompatibility complex-restricted manner. We conclude that the antiviral pulmonary immune response is a collaborative function that involves many antigenic peptides, among which the IE1 peptide is immunodominant in a relative sense.

* Corresponding author. Mailing address: Institute for Virology, Johannes Gutenberg-University, Hochhaus am Augustusplatz, 55101 Mainz, Germany. Phone: 49-6131-173650. Fax: 49-6131-395604. E-mail: REDDEHAS{at}mzdmza.zdv.uni-mainz.de

Journal of Virology, September 1998, p. 7201-7212, Vol. 72, No. 9
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Bohm, V., Seckert, C. K., Simon, C. O., Thomas, D., Renzaho, A., Gendig, D., Holtappels, R., Reddehase, M. J. (2009). Immune Evasion Proteins Enhance Cytomegalovirus Latency in the Lungs. J. Virol. 83: 10293-10298 [Abstract] [Full Text]  
  • Seckert, C. K., Renzaho, A., Tervo, H.-M., Krause, C., Deegen, P., Kuhnapfel, B., Reddehase, M. J., Grzimek, N. K. A. (2009). Liver Sinusoidal Endothelial Cells Are a Site of Murine Cytomegalovirus Latency and Reactivation. J. Virol. 83: 8869-8884 [Abstract] [Full Text]  
  • Pipeling, M. R., West, E. E., Osborne, C. M., Whitlock, A. B., Dropulic, L. K., Willett, M. H., Forman, M., Valsamakis, A., Orens, J. B., Moller, D. R., Lechtzin, N., Migueles, S. A., Connors, M., McDyer, J. F. (2008). Differential CMV-Specific CD8+ Effector T Cell Responses in the Lung Allograft Predominate over the Blood during Human Primary Infection. J. Immunol. 181: 546-556 [Abstract] [Full Text]  
  • Munks, M. W., Pinto, A. K., Doom, C. M., Hill, A. B. (2007). Viral Interference with Antigen Presentation Does Not Alter Acute or Chronic CD8 T Cell Immunodominance in Murine Cytomegalovirus Infection. J. Immunol. 178: 7235-7241 [Abstract] [Full Text]  
  • Simon, C. O., Holtappels, R., Tervo, H.-M., Bohm, V., Daubner, T., Oehrlein-Karpi, S. A., Kuhnapfel, B., Renzaho, A., Strand, D., Podlech, J., Reddehase, M. J., Grzimek, N. K. A. (2006). CD8 T Cells Control Cytomegalovirus Latency by Epitope-Specific Sensing of Transcriptional Reactivation. J. Virol. 80: 10436-10456 [Abstract] [Full Text]  
  • Erlach, K. C., Bohm, V., Seckert, C. K., Reddehase, M. J., Podlech, J. (2006). Lymphoma cell apoptosis in the liver induced by distant murine cytomegalovirus infection.. J. Virol. 80: 4801-4819 [Abstract] [Full Text]  
  • Singbartl, K., Bockhorn, S. G.{b.}e, Zarbock, A., Schmolke, M., Van Aken, H. (2005). T Cells Modulate Neutrophil-Dependent Acute Renal Failure during Endotoxemia: Critical Role for CD28. J. Am. Soc. Nephrol. 16: 720-728 [Abstract] [Full Text]  
  • Morello, C. S., Ye, M., Hung, S., Kelley, L. A., Spector, D. H. (2005). Systemic Priming-Boosting Immunization with a Trivalent Plasmid DNA and Inactivated Murine Cytomegalovirus (MCMV) Vaccine Provides Long-Term Protection against Viral Replication following Systemic or Mucosal MCMV Challenge. J. Virol. 79: 159-175 [Abstract] [Full Text]  
  • Simon, C. O., Seckert, C. K., Dreis, D., Reddehase, M. J., Grzimek, N. K. A. (2005). Role for Tumor Necrosis Factor Alpha in Murine Cytomegalovirus Transcriptional Reactivation in Latently Infected Lungs. J. Virol. 79: 326-340 [Abstract] [Full Text]  
  • Ye, M., Morello, C. S., Spector, D. H. (2004). Multiple Epitopes in the Murine Cytomegalovirus Early Gene Product M84 Are Efficiently Presented in Infected Primary Macrophages and Contribute to Strong CD8+-T-Lymphocyte Responses and Protection following DNA Immunization. J. Virol. 78: 11233-11245 [Abstract] [Full Text]  
  • Manley, T. J., Luy, L., Jones, T., Boeckh, M., Mutimer, H., Riddell, S. R. (2004). Immune evasion proteins of human cytomegalovirus do not prevent a diverse CD8+ cytotoxic T-cell response in natural infection. Blood 104: 1075-1082 [Abstract] [Full Text]  
  • Gibson, L., Piccinini, G., Lilleri, D., Revello, M. G., Wang, Z., Markel, S., Diamond, D. J., Luzuriaga, K. (2004). Human Cytomegalovirus Proteins pp65 and Immediate Early Protein 1 Are Common Targets for CD8+ T Cell Responses in Children with Congenital or Postnatal Human Cytomegalovirus Infection. J. Immunol. 172: 2256-2264 [Abstract] [Full Text]  
  • Cavanaugh, V. J., Deng, Y., Birkenbach, M. P., Slater, J. S., Campbell, A. E. (2003). Vigorous Innate and Virus-Specific Cytotoxic T-Lymphocyte Responses to Murine Cytomegalovirus in the Submaxillary Salivary Gland. J. Virol. 77: 1703-1717 [Abstract] [Full Text]  
  • Skoberne, M., Schenk, S., Hof, H., Geginat, G. (2002). Cross-Presentation of Listeria monocytogenes-Derived CD4 T Cell Epitopes. J. Immunol. 169: 1410-1418 [Abstract] [Full Text]  
  • Gold, M. C., Munks, M. W., Wagner, M., Koszinowski, U. H., Hill, A. B., Fling, S. P. (2002). The Murine Cytomegalovirus Immunomodulatory Gene m152 Prevents Recognition of Infected Cells by M45-Specific CTL But Does Not Alter the Immunodominance of the M45-Specific CD8 T Cell Response In Vivo. J. Immunol. 169: 359-365 [Abstract] [Full Text]  
  • Holtappels, R., Grzimek, N. K. A., Simon, C. O., Thomas, D., Dreis, D., Reddehase, M. J. (2002). Processing and Presentation of Murine Cytomegalovirus pORFm164-Derived Peptide in Fibroblasts in the Face of All Viral Immunosubversive Early Gene Functions. J. Virol. 76: 6044-6053 [Abstract] [Full Text]  
  • Morello, C. S., Ye, M., Spector, D. H. (2002). Development of a Vaccine against Murine Cytomegalovirus (MCMV), Consisting of Plasmid DNA and Formalin-Inactivated MCMV, That Provides Long-Term, Complete Protection against Viral Replication. J. Virol. 76: 4822-4835 [Abstract] [Full Text]  
  • Ye, M., Morello, C. S., Spector, D. H. (2002). Strong CD8 T-Cell Responses following Coimmunization with Plasmids Expressing the Dominant pp89 and Subdominant M84 Antigens of Murine Cytomegalovirus Correlate with Long-Term Protection against Subsequent Viral Challenge. J. Virol. 76: 2100-2112 [Abstract] [Full Text]  
  • Erlach, K. C., Podlech, J., Rojan, A., Reddehase, M. J. (2002). Tumor Control in a Model of Bone Marrow Transplantation and Acute Liver-Infiltrating B-Cell Lymphoma: an Unpredicted Novel Function of Cytomegalovirus. J. Virol. 76: 2857-2870 [Abstract] [Full Text]  
  • Skoberne, M., Geginat, G. (2002). Efficient In Vivo Presentation of Listeria monocytogenes- Derived CD4 and CD8 T Cell Epitopes in the Absence of IFN-{gamma}. J. Immunol. 168: 1854-1860 [Abstract] [Full Text]  
  • Holtappels, R., Grzimek, N. K. A., Thomas, D., Reddehase, M. J. (2002). Early gene m18, a novel player in the immune response to murine cytomegalovirus. J. Gen. Virol. 83: 311-316 [Abstract] [Full Text]  
  • Holtappels, R., Thomas, D., Podlech, J., Reddehase, M. J. (2002). Two Antigenic Peptides from Genes m123 and m164 of Murine Cytomegalovirus Quantitatively Dominate CD8 T-Cell Memory in the H-2d Haplotype. J. Virol. 76: 151-164 [Abstract] [Full Text]  
  • Holtappels, R., Podlech, J., Grzimek, N. K. A., Thomas, D., Pahl-Seibert, M.-F., Reddehase, M. J. (2001). Experimental Preemptive Immunotherapy of Murine Cytomegalovirus Disease with CD8 T-Cell Lines Specific for ppM83 and pM84, the Two Homologs of Human Cytomegalovirus Tegument Protein ppUL83 (pp65). J. Virol. 75: 6584-6600 [Abstract] [Full Text]  
  • Grzimek, N. K. A., Dreis, D., Schmalz, S., Reddehase, M. J. (2001). Random, Asynchronous, and Asymmetric Transcriptional Activity of Enhancer-Flanking Major Immediate-Early Genes ie1/3 and ie2 during Murine Cytomegalovirus Latency in the Lungs. J. Virol. 75: 2692-2705 [Abstract] [Full Text]  
  • Holtappels, R., Pahl-Seibert, M.-F., Thomas, D., Reddehase, M. J. (2000). Enrichment of Immediate-Early 1 (m123/pp89) Peptide-Specific CD8 T Cells in a Pulmonary CD62Llo Memory-Effector Cell Pool during Latent Murine Cytomegalovirus Infection of the Lungs. J. Virol. 74: 11495-11503 [Abstract] [Full Text]  
  • Holtappels, R., Thomas, D., Reddehase, M. J. (2000). Identification of a Kd-restricted antigenic peptide encoded by murine cytomegalovirus early gene M84. J. Gen. Virol. 81: 3037-3042 [Abstract] [Full Text]  
  • Podlech, J., Holtappels, R., Pahl-Seibert, M.-F., Steffens, H.-P., Reddehase, M. J. (2000). Murine Model of Interstitial Cytomegalovirus Pneumonia in Syngeneic Bone Marrow Transplantation: Persistence of Protective Pulmonary CD8-T-Cell Infiltrates after Clearance of Acute Infection. J. Virol. 74: 7496-7507 [Abstract] [Full Text]  
  • Pepperl, S., Münster, J., Mach, M., Harris, J. R., Plachter, B. (2000). Dense Bodies of Human Cytomegalovirus Induce both Humoral and Cellular Immune Responses in the Absence of Viral Gene Expression. J. Virol. 74: 6132-6146 [Abstract] [Full Text]  
  • Morello, C. S., Cranmer, L. D., Spector, D. H. (2000). Suppression of Murine Cytomegalovirus (MCMV) Replication with a DNA Vaccine Encoding MCMV M84 (a Homolog of Human Cytomegalovirus pp65). J. Virol. 74: 3696-3708 [Abstract] [Full Text]  
  • Holtappels, R., Thomas, D., Podlech, J., Geginat, G., Steffens, H.-P., Reddehase, M. J. (2000). The Putative Natural Killer Decoy Early Gene m04 (gp34) of Murine Cytomegalovirus Encodes an Antigenic Peptide Recognized by Protective Antiviral CD8 T Cells. J. Virol. 74: 1871-1884 [Abstract] [Full Text]  
  • Kurz, S. K., Reddehase, M. J. (1999). Patchwork Pattern of Transcriptional Reactivation in the Lungs Indicates Sequential Checkpoints in the Transition from Murine Cytomegalovirus Latency to Recurrence. J. Virol. 73: 8612-8622 [Abstract] [Full Text]  
  • Morello, C. S., Cranmer, L. D., Spector, D. H. (1999). In Vivo Replication, Latency, and Immunogenicity of Murine Cytomegalovirus Mutants with Deletions in the M83 and M84 Genes, the Putative Homologs of Human Cytomegalovirus pp65 (UL83). J. Virol. 73: 7678-7693 [Abstract] [Full Text]  
  • Kurz, S. K., Rapp, M., Steffens, H.-P., Grzimek, N. K. A., Schmalz, S., Reddehase, M. J. (1999). Focal Transcriptional Activity of Murine Cytomegalovirus during Latency in the Lungs. J. Virol. 73: 482-494 [Abstract] [Full Text]  
  • Alterio de Goss, M., Holtappels, R., Steffens, H.-P., Podlech, J., Angele, P., Dreher, L., Thomas, D., Reddehase, M. J. (1998). Control of Cytomegalovirus in Bone Marrow Transplantation Chimeras Lacking the Prevailing Antigen-Presenting Molecule in Recipient Tissues Rests Primarily on Recipient-Derived CD8 T Cells. J. Virol. 72: 7733-7744 [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»