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
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
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 Ou, R.
Right arrow Articles by Moskophidis, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ou, R.
Right arrow Articles by Moskophidis, D.

 Previous Article  |  Next Article 

Journal of Virology, September 2001, p. 8407-8423, Vol. 75, No. 18
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.18.8407-8423.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Critical Role for Alpha/Beta and Gamma Interferons in Persistence of Lymphocytic Choriomeningitis Virus by Clonal Exhaustion of Cytotoxic T Cells

Rong Ou, Shenghua Zhou, Lei Huang, and Demetrius Moskophidis*

Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia 30912

Received 3 April 2001/Accepted 11 June 2001

Under conditions of high antigenic load during infection with invasive lymphocytic choriomeningitis virus (LCMV) strains, virus can persist by selective clonal exhaustion of antigen-specific CD8+ T cells. In this work we studied the down-regulation of the virus-specific CD8+-T-cell response during a persistent infection of adult mice, with particular emphasis on the contribution of the interferon response in promoting host defense. Studies were conducted by infecting mice deficient in receptors for type I (alpha/beta interferon [IFN-alpha /beta ]), type II (IFN-gamma ), and both type I and II IFNs with LCMV isolates that vary in their capacity to induce T-cell exhaustion. The main conclusions of this study are as follows. (i) IFNs play a critical role in LCMV infection by reducing viral loads in the initial stages of infection and thus modifying both the extent of CD8+-T-cell exhaustion and the course of infection. The importance of IFNs in this context varies with the biological properties of the LCMV strain. (ii) An inverse correlation exists between antigen persistence and responsiveness of virus-specific CD8+ T cells. This results in distinct programs of activation or tolerance (functional unresponsiveness and/or physical elimination of antigen-specific cells) during acute and chronic virus infections, respectively. (iii) A successful immune response associated with definitive viral clearance requires an appropriate balance between cellular and humoral components of the immune system. We discuss the role of IFNs in influencing virus-specific T cells that determine the outcome of persistent infections.

* Corresponding author. Mailing address: Institute of Molecular Medicine and Genetics, Medical College of Georgia, 1120 15th St., CB-2803, Augusta, GA 30912-3175. Phone: (706) 721-8738. Fax: (706) 721-8732. E-mail: moskophidis{at}immag.mcg.edu.

Journal of Virology, September 2001, p. 8407-8423, Vol. 75, No. 18
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.18.8407-8423.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Basler, M., Lauer, C., Beck, U., Groettrup, M. (2009). The Proteasome Inhibitor Bortezomib Enhances the Susceptibility to Viral Infection. J. Immunol. 183: 6145-6150 [Abstract] [Full Text]  
  • Elsaesser, H., Sauer, K., Brooks, D. G. (2009). IL-21 Is Required to Control Chronic Viral Infection. Science 324: 1569-1572 [Abstract] [Full Text]  
  • Lee, L. N., Burke, S., Montoya, M., Borrow, P. (2009). Multiple Mechanisms Contribute to Impairment of Type 1 Interferon Production during Chronic Lymphocytic Choriomeningitis Virus Infection of Mice. J. Immunol. 182: 7178-7189 [Abstract] [Full Text]  
  • Xiao, Z., Casey, K. A., Jameson, S. C., Curtsinger, J. M., Mescher, M. F. (2009). Programming for CD8 T Cell Memory Development Requires IL-12 or Type I IFN. J. Immunol. 182: 2786-2794 [Abstract] [Full Text]  
  • Zhou, S., Kurt-Jones, E. A., Cerny, A. M., Chan, M., Bronson, R. T., Finberg, R. W. (2009). MyD88 Intrinsically Regulates CD4 T-Cell Responses. J. Virol. 83: 1625-1634 [Abstract] [Full Text]  
  • Liu, B., Woltman, A. M., Janssen, H. L. A., Boonstra, A. (2009). Modulation of dendritic cell function by persistent viruses. J. Leukoc. Biol. 85: 205-214 [Abstract] [Full Text]  
  • Mauermann, N., Burian, J., von Garnier, C., Dirnhofer, S., Germano, D., Schuett, C., Tamm, M., Bingisser, R., Eriksson, U., Hunziker, L. (2008). Interferon-{gamma} Regulates Idiopathic Pneumonia Syndrome, a Th17+CD4+ T-Cell-mediated Graft-versus-Host Disease. Am. J. Respir. Crit. Care Med. 178: 379-388 [Abstract] [Full Text]  
  • Chen, M., Lan, S., Ou, R., Price, G. E., Jiang, H., de la Torre, J. C., Moskophidis, D. (2008). Genomic and biological characterization of aggressive and docile strains of lymphocytic choriomeningitis virus rescued from a plasmid-based reverse-genetics system. J. Gen. Virol. 89: 1421-1433 [Abstract] [Full Text]  
  • Ou, R., Zhang, M., Huang, L., Moskophidis, D. (2008). Control of Virus-Specific CD8+ T-Cell Exhaustion and Immune-Mediated Pathology by E3 Ubiquitin Ligase Cbl-b during Chronic Viral Infection. J. Virol. 82: 3353-3368 [Abstract] [Full Text]  
  • Ha, S.-J., Mueller, S. N., Wherry, E. J., Barber, D. L., Aubert, R. D., Sharpe, A. H., Freeman, G. J., Ahmed, R. (2008). Enhancing therapeutic vaccination by blocking PD-1-mediated inhibitory signals during chronic infection. JEM 205: 543-555 [Abstract] [Full Text]  
  • Ou, R., Zhang, M., Huang, L., Flavell, R. A., Koni, P. A., Moskophidis, D. (2008). Regulation of Immune Response and Inflammatory Reactions against Viral Infection by VCAM-1. J. Virol. 82: 2952-2965 [Abstract] [Full Text]  
  • Jung, A., Kato, H., Kumagai, Y., Kumar, H., Kawai, T., Takeuchi, O., Akira, S. (2008). Lymphocytoid Choriomeningitis Virus Activates Plasmacytoid Dendritic Cells and Induces a Cytotoxic T-Cell Response via MyD88. J. Virol. 82: 196-206 [Abstract] [Full Text]  
  • Belnoue, E., Fontannaz-Bozzotti, P., Grillet, S., Lambert, P.-H., Siegrist, C.-A. (2007). Protracted Course of Lymphocytic Choriomeningitis Virus WE Infection in Early Life: Induction but Limited Expansion of CD8+ Effector T Cells and Absence of Memory CD8+ T Cells. J. Virol. 81: 7338-7350 [Abstract] [Full Text]  
  • Zhou, S., Kurt-Jones, E. A., Fitzgerald, K. A., Wang, J. P., Cerny, A. M., Chan, M., Finberg, R. W. (2007). Role of MyD88 in Route-Dependent Susceptibility to Vesicular Stomatitis Virus Infection. J. Immunol. 178: 5173-5181 [Abstract] [Full Text]  
  • Brown, B. D., Sitia, G., Annoni, A., Hauben, E., Sergi, L. S., Zingale, A., Roncarolo, M. G., Guidotti, L. G., Naldini, L. (2007). In vivo administration of lentiviral vectors triggers a type I interferon response that restricts hepatocyte gene transfer and promotes vector clearance. Blood 109: 2797-2805 [Abstract] [Full Text]  
  • Agnellini, P., Wolint, P., Rehr, M., Cahenzli, J., Karrer, U., Oxenius, A. (2007). Impaired NFAT nuclear translocation results in split exhaustion of virus-specific CD8+ T cell functions during chronic viral infection. Proc. Natl. Acad. Sci. USA 104: 4565-4570 [Abstract] [Full Text]  
  • Van Dyken, S. J., Green, R. S., Marth, J. D. (2007). Structural and Mechanistic Features of Protein O Glycosylation Linked to CD8+ T-Cell Apoptosis. Mol. Cell. Biol. 27: 1096-1111 [Abstract] [Full Text]  
  • Wang, Y., Lobigs, M., Lee, E., Koskinen, A., Mullbacher, A. (2006). CD8+ T cell-mediated immune responses in West Nile virus (Sarafend strain) encephalitis are independent of gamma interferon. J. Gen. Virol. 87: 3599-3609 [Abstract] [Full Text]  
  • Kunz, S., Rojek, J. M., Roberts, A. J., McGavern, D. B., Oldstone, M. B. A., de la Torre, J. C. (2006). Altered Central Nervous System Gene Expression Caused by Congenitally Acquired Persistent Infection with Lymphocytic Choriomeningitis Virus. J. Virol. 80: 9082-9092 [Abstract] [Full Text]  
  • Bertoletti, A., Gehring, A. J. (2006). The immune response during hepatitis B virus infection. J. Gen. Virol. 87: 1439-1449 [Abstract] [Full Text]  
  • Ank, N., West, H., Bartholdy, C., Eriksson, K., Thomsen, A. R., Paludan, S. R. (2006). Lambda Interferon (IFN-{lambda}), a Type III IFN, Is Induced by Viruses and IFNs and Displays Potent Antiviral Activity against Select Virus Infections In Vivo. J. Virol. 80: 4501-4509 [Abstract] [Full Text]  
  • Lopez, C. B., Yount, J. S., Hermesh, T., Moran, T. M. (2006). Sendai Virus Infection Induces Efficient Adaptive Immunity Independently of Type I Interferons. J. Virol. 80: 4538-4545 [Abstract] [Full Text]  
  • Aichele, P., Unsoeld, H., Koschella, M., Schweier, O., Kalinke, U., Vucikuja, S. (2006). Cutting edge: CD8 T cells specific for lymphocytic choriomeningitis virus require type I IFN receptor for clonal expansion.. J. Immunol. 176: 4525-4529 [Abstract] [Full Text]  
  • Lopez, C. B., Yount, J. S., Moran, T. M. (2006). Toll-Like Receptor-Independent Triggering of Dendritic Cell Maturation by Viruses. J. Virol. 80: 3128-3134 [Full Text]  
  • Rouzine, I. M., Sergeev, R. A., Glushtsov, A. I. (2006). Two types of cytotoxic lymphocyte regulation explain kinetics of immune response to human immunodeficiency virus. Proc. Natl. Acad. Sci. USA 103: 666-671 [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]  
  • Kolumam, G. A., Thomas, S., Thompson, L. J., Sprent, J., Murali-Krishna, K. (2005). Type I interferons act directly on CD8 T cells to allow clonal expansion and memory formation in response to viral infection. JEM 202: 637-650 [Abstract] [Full Text]  
  • Henrichsen, P., Bartholdy, C., Christensen, J. P., Thomsen, A. R. (2005). Impaired Virus Control and Severe CD8+ T-Cell-Mediated Immunopathology in Chimeric Mice Deficient in Gamma Interferon Receptor Expression on both Parenchymal and Hematopoietic Cells. J. Virol. 79: 10073-10076 [Abstract] [Full Text]  
  • Ousman, S. S., Wang, J., Campbell, I. L. (2005). Differential Regulation of Interferon Regulatory Factor (IRF)-7 and IRF-9 Gene Expression in the Central Nervous System during Viral Infection. J. Virol. 79: 7514-7527 [Abstract] [Full Text]  
  • Gowen, B. B., Barnard, D. L., Smee, D. F., Wong, M.-H., Pace, A. M., Jung, K.-H., Winslow, S. G., Bailey, K. W., Blatt, L. M., Sidwell, R. W. (2005). Interferon Alfacon-1 Protects Hamsters from Lethal Pichinde Virus Infection. Antimicrob. Agents Chemother. 49: 2378-2386 [Abstract] [Full Text]  
  • Silvestri, G., Fedanov, A., Germon, S., Kozyr, N., Kaiser, W. J., Garber, D. A., McClure, H., Feinberg, M. B., Staprans, S. I. (2005). Divergent Host Responses during Primary Simian Immunodeficiency Virus SIVsm Infection of Natural Sooty Mangabey and Nonnatural Rhesus Macaque Hosts. J. Virol. 79: 4043-4054 [Abstract] [Full Text]  
  • Montoya, M., Edwards, M. J., Reid, D. M., Borrow, P. (2005). Rapid Activation of Spleen Dendritic Cell Subsets following Lymphocytic Choriomeningitis Virus Infection of Mice: Analysis of the Involvement of Type 1 IFN. J. Immunol. 174: 1851-1861 [Abstract] [Full Text]  
  • Pannetier, D., Faure, C., Georges-Courbot, M.-C., Deubel, V., Baize, S. (2004). Human Macrophages, but Not Dendritic Cells, Are Activated and Produce Alpha/Beta Interferons in Response to Mopeia Virus Infection. J. Virol. 78: 10516-10524 [Abstract] [Full Text]  
  • Jordan, M. B., Hildeman, D., Kappler, J., Marrack, P. (2004). An animal model of hemophagocytic lymphohistiocytosis (HLH): CD8+ T cells and interferon gamma are essential for the disorder. Blood 104: 735-743 [Abstract] [Full Text]  
  • Homann, D., McGavern, D. B., Oldstone, M. B. A. (2004). Visualizing the Viral Burden: Phenotypic and Functional Alterations of T Cells and APCs during Persistent Infection. J. Immunol. 172: 6239-6250 [Abstract] [Full Text]  
  • Zhou, S., Ou, R., Huang, L., Price, G. E., Moskophidis, D. (2004). Differential Tissue-Specific Regulation of Antiviral CD8+ T-Cell Immune Responses during Chronic Viral Infection. J. Virol. 78: 3578-3600 [Abstract] [Full Text]  
  • Fuller, M. J., Khanolkar, A., Tebo, A. E., Zajac, A. J. (2004). Maintenance, Loss, and Resurgence of T Cell Responses During Acute, Protracted, and Chronic Viral Infections. J. Immunol. 172: 4204-4214 [Abstract] [Full Text]  
  • Asper, M., Sternsdorf, T., Hass, M., Drosten, C., Rhode, A., Schmitz, H., Gunther, S. (2004). Inhibition of Different Lassa Virus Strains by Alpha and Gamma Interferons and Comparison with a Less Pathogenic Arenavirus. J. Virol. 78: 3162-3169 [Abstract] [Full Text]  
  • Khanolkar, A., Fuller, M. J., Zajac, A. J. (2004). CD4 T Cell-Dependent CD8 T Cell Maturation. J. Immunol. 172: 2834-2844 [Abstract] [Full Text]  
  • Tewari, K., Sacha, J., Gao, X., Suresh, M. (2004). Effect of Chronic Viral Infection on Epitope Selection, Cytokine Production, and Surface Phenotype of CD8 T Cells and the Role of IFN-{gamma} Receptor in Immune Regulation. J. Immunol. 172: 1491-1500 [Abstract] [Full Text]  
  • He, C., Schenk, S., Zhang, Q., Valujskikh, A., Bayer, J., Fairchild, R. L., Heeger, P. S. (2004). Effects of T Cell Frequency and Graft Size on Transplant Outcome in Mice. J. Immunol. 172: 240-247 [Abstract] [Full Text]  
  • Wherry, E. J., Blattman, J. N., Murali-Krishna, K., van der Most, R., Ahmed, R. (2003). Viral Persistence Alters CD8 T-Cell Immunodominance and Tissue Distribution and Results in Distinct Stages of Functional Impairment. J. Virol. 77: 4911-4927 [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]  
  • Fuller, M. J., Zajac, A. J. (2003). Ablation of CD8 and CD4 T Cell Responses by High Viral Loads. J. Immunol. 170: 477-486 [Abstract] [Full Text]  
  • Hunziker, L., Recher, M., Ciurea, A., Martinic, M. M.A., Odermatt, B., Hengartner, H., Zinkernagel, R. M. (2002). Antagonistic Variant Virus Prevents Wild-type Virus-induced Lethal Immunopathology. JEM 196: 1039-1046 [Abstract] [Full Text]  
  • Zhou, S., Ou, R., Huang, L., Moskophidis, D. (2002). Critical Role for Perforin-, Fas/FasL-, and TNFR1-Mediated Cytotoxic Pathways in Down-Regulation of Antigen-Specific T Cells during Persistent Viral Infection. J. Virol. 76: 829-840 [Abstract] [Full Text]  
  • Reignat, S., Webster, G. J.M., Brown, D., Ogg, G. S., King, A., Seneviratne, S. L., Dusheiko, G., Williams, R., Maini, M. K., Bertoletti, A. (2002). Escaping High Viral Load Exhaustion: CD8 Cells with Altered Tetramer Binding in Chronic Hepatitis B Virus Infection. JEM 195: 1089-1101 [Abstract] [Full Text]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»