Immunosuppression and Resultant Viral Persistence by Specific Viral Targeting of Dendritic Cells

doi:10.1084/jem.192.9.1249

Published online 30 October 2000.

This Article

	Full Text
	Full Text (PDF, 486K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Sevilla, N.
	Articles by Oldstone, M. B.A.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Sevilla, N.
	Articles by Oldstone, M. B.A.


Social Bookmarking

	What's this?

© The Rockefeller University Press, 0022-1007/2000/11/1249/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 9, November 6, 2000 1249-1260

Original Article

Immunosuppression and Resultant Viral Persistence by Specific Viral Targeting of Dendritic Cells

Noemí Sevilla^a, Stefan Kunz^a, Andreas Holz^a, Hanna Lewicki^a, Dirk Homann^a, Hiroki Yamada^b, Kevin P. Campbell^b, Juan C. de la Torre^a, and Michael B.A. Oldstone^a
^a Department of Neuropharmacology, Division of Virology, The Scripps Research Institute, La Jolla, California 92037
^b Department of Physiology and Biophysics, Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, Iowa 52242

Correspondence to: Michael B.A. Oldstone, Division of Virology, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037. Tel:858-784 8054 Fax:858-784 9981

Among cells of the immune system, CD11c⁺ and DEC-205⁺ splenicdendritic cells primarily express the cellular receptor ( ${alpha}$ -dystroglycan[ ${alpha}$ -DG]) for lymphocytic choriomeningitis virus (LCMV). By selection,strains and variants of LCMV that bind ${alpha}$ -DG with high affinityare associated with virus replication in the white pulp, showpreferential replication in a majority of CD11c⁺ and DEC-205⁺cells, cause immunosuppression, and establish a persistent infection.In contrast, viral strains and variants that bind with low affinityto ${alpha}$ -DG are associated with viral replication in the red pulp,display minimal replication in CD11c⁺ and DEC-205⁺ cells, andgenerate a robust anti-LCMV cytotoxic T lymphocyte responsethat clears the virus infection. Differences in binding affinitiescan be mapped to a single amino acid change in the viral glycoprotein1 ligand that binds to ${alpha}$ -DG. These findings indicate that receptor–virusinteraction on dendritic cells in vivo can be an essential stepin the initiation of virus-induced immunosuppression and viralpersistence.

Key Words: lymphocytic choriomeningitis virus, CD11c⁺/DEC-205⁺ cells, tropism,viral receptor, selection

Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

Mueller, S. N., Ahmed, R. (2009). High antigen levels are the cause of T cell exhaustion during chronic viral infection. Proc. Natl. Acad. Sci. USA 106: 8623-8628 [Abstract] [Full Text]
Coppieters, K., Barral, A. M., Juedes, A., Wolfe, T., Rodrigo, E., Thery, C., Amigorena, S., von Herrath, M. G. (2009). No Significant CTL Cross-Priming by Dendritic Cell-Derived Exosomes during Murine Lymphocytic Choriomeningitis Virus Infection. J. Immunol. 182: 2213-2220 [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]
Chase, J. C., Celli, J., Bosio, C. M. (2009). Direct and Indirect Impairment of Human Dendritic Cell Function by Virulent Francisella tularensis Schu S4. Infect. Immun. 77: 180-195 [Abstract] [Full Text]
Imperiali, M., Sporri, R., Hewitt, J., Oxenius, A. (2008). Post-translational modification of {alpha}-dystroglycan is not critical for lymphocytic choriomeningitis virus receptor function in vivo. J. Gen. Virol. 89: 2713-2722 [Abstract] [Full Text]
Kamimura, D., Bevan, M. J. (2008). Endoplasmic Reticulum Stress Regulator XBP-1 Contributes to Effector CD8+ T Cell Differentiation during Acute Infection. J. Immunol. 181: 5433-5441 [Abstract] [Full Text]
Dauner, J. G., Williams, I. R., Jacob, J. (2008). Differential Microenvironment Localization of Effector and Memory CD8 T Cells. J. Immunol. 180: 291-299 [Abstract] [Full Text]
Rojek, J. M., Campbell, K. P., Oldstone, M. B.A., Kunz, S. (2007). Old World Arenavirus Infection Interferes with the Expression of Functional {alpha}-Dystroglycan in the Host Cell. Mol. Biol. Cell 18: 4493-4507 [Abstract] [Full Text]
Mueller, S. N., Matloubian, M., Clemens, D. M., Sharpe, A. H., Freeman, G. J., Gangappa, S., Larsen, C. P., Ahmed, R. (2007). Viral targeting of fibroblastic reticular cells contributes to immunosuppression and persistence during chronic infection. Proc. Natl. Acad. Sci. USA 104: 15430-15435 [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]
Bergthaler, A., Merkler, D., Horvath, E., Bestmann, L., Pinschewer, D. D. (2007). Contributions of the lymphocytic choriomeningitis virus glycoprotein and polymerase to strain-specific differences in murine liver pathogenicity. J. Gen. Virol. 88: 592-603 [Abstract] [Full Text]
Bartholdy, C., Kauffmann, S. O., Christensen, J. P., Thomsen, A. R. (2007). Agonistic Anti-CD40 Antibody Profoundly Suppresses the Immune Response to Infection with Lymphocytic Choriomeningitis Virus. J. Immunol. 178: 1662-1670 [Abstract] [Full Text]
Ejrnaes, M., Filippi, C. M., Martinic, M. M., Ling, E. M., Togher, L. M., Crotty, S., von Herrath, M. G. (2006). Resolution of a chronic viral infection after interleukin-10 receptor blockade. JEM 203: 2461-2472 [Abstract] [Full Text]
Schneider-Schaulies, S., Dittmer, U. (2006). Silencing T cells or T-cell silencing: concepts in virus-induced immunosuppression. J. Gen. Virol. 87: 1423-1438 [Abstract] [Full Text]
Flatz, L., Bergthaler, A., de la Torre, J. C., Pinschewer, D. D. (2006). Recovery of an arenavirus entirely from RNA polymerase I/II-driven cDNA. Proc. Natl. Acad. Sci. USA 103: 4663-4668 [Abstract] [Full Text]
Diaz-San Segundo, F., Salguero, F. J., de Avila, A., Fernandez de Marco, M. M., Sanchez-Martin, M. A., Sevilla, N. (2006). Selective Lymphocyte Depletion during the Early Stage of the Immune Response to Foot-and-Mouth Disease Virus Infection in Swine. J. Virol. 80: 2369-2379 [Abstract] [Full Text]
Zhou, H., Perlman, S. (2006). Preferential Infection of Mature Dendritic Cells by Mouse Hepatitis Virus Strain JHM. J. Virol. 80: 2506-2514 [Abstract] [Full Text]
Homann, D., Dummer, W., Wolfe, T., Rodrigo, E., Theofilopoulos, A. N., Oldstone, M. B. A., von Herrath, M. G. (2006). Lack of Intrinsic CTLA-4 Expression Has Minimal Effect on Regulation of Antiviral T-Cell Immunity. J. Virol. 80: 270-280 [Abstract] [Full Text]
Kunz, S., Rojek, J. M., Kanagawa, M., Spiropoulou, C. F., Barresi, R., Campbell, K. P., Oldstone, M. B. A. (2005). Posttranslational Modification of {alpha}-Dystroglycan, the Cellular Receptor for Arenaviruses, by the Glycosyltransferase LARGE Is Critical for Virus Binding. J. Virol. 79: 14282-14296 [Abstract] [Full Text]
Imperiali, M., Thoma, C., Pavoni, E., Brancaccio, A., Callewaert, N., Oxenius, A. (2005). O Mannosylation of {alpha}-Dystroglycan Is Essential for Lymphocytic Choriomeningitis Virus Receptor Function. J. Virol. 79: 14297-14308 [Abstract] [Full Text]
Oldstone, M. B.A., Dales, S., Tishon, A., Lewicki, H., Martin, L. (2005). A role for dual viral hits in causation of subacute sclerosing panencephalitis. JEM 202: 1185-1190 [Abstract] [Full Text]
Flano, E., Kayhan, B., Woodland, D. L., Blackman, M. A. (2005). Infection of Dendritic Cells by a {gamma}2-Herpesvirus Induces Functional Modulation. J. Immunol. 175: 3225-3234 [Abstract] [Full Text]
Brooks, D. G., Teyton, L., Oldstone, M. B. A., McGavern, D. B. (2005). Intrinsic Functional Dysregulation of CD4 T Cells Occurs Rapidly following Persistent Viral Infection. J. Virol. 79: 10514-10527 [Abstract] [Full Text]
Wherry, E. J., Blattman, J. N., Ahmed, R. (2005). Low CD8 T-Cell Proliferative Potential and High Viral Load Limit the Effectiveness of Therapeutic Vaccination. J. Virol. 79: 8960-8968 [Abstract] [Full Text]
Belz, G. T., Shortman, K., Bevan, M. J., Heath, W. R. (2005). CD8{alpha}+ Dendritic Cells Selectively Present MHC Class I-Restricted Noncytolytic Viral and Intracellular Bacterial Antigens In Vivo. J. Immunol. 175: 196-200 [Abstract] [Full Text]
Kunz, S., Rojek, J. M., Perez, M., Spiropoulou, C. F., Oldstone, M. B. A. (2005). Characterization of the Interaction of Lassa Fever Virus with Its Cellular Receptor {alpha}-Dystroglycan. J. Virol. 79: 5979-5987 [Abstract] [Full Text]
Probst, H. C., van den Broek, M. (2005). Priming of CTLs by Lymphocytic Choriomeningitis Virus Depends on Dendritic Cells. J. Immunol. 174: 3920-3924 [Abstract] [Full Text]
Chen, M., Barnfield, C., Naslund, T. I., Fleeton, M. N., Liljestrom, P. (2005). MyD88 Expression Is Required for Efficient Cross-Presentation of Viral Antigens from Infected Cells. J. Virol. 79: 2964-2972 [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]
Martino, A., Sacchi, A., Sanarico, N., Spadaro, F., Ramoni, C., Ciaramella, A., Pucillo, L. P., Colizzi, V., Vendetti, S. (2004). Dendritic cells derived from BCG-infected precursors induce Th2-like immune response. J. Leukoc. Biol. 76: 827-834 [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]
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]
Baize, S., Kaplon, J., Faure, C., Pannetier, D., Georges-Courbot, M.-C., Deubel, V. (2004). Lassa Virus Infection of Human Dendritic Cells and Macrophages Is Productive but Fails to Activate Cells. J. Immunol. 172: 2861-2869 [Abstract] [Full Text]
Rambukkana, A., Kunz, S., Min, J., Campbell, K. P., Oldstone, M. B. A. (2003). Targeting Schwann cells by nonlytic arenaviral infection selectively inhibits myelination. Proc. Natl. Acad. Sci. USA 100: 16071-16076 [Abstract] [Full Text]
Geisbert, T. W., Hensley, L. E., Larsen, T., Young, H. A., Reed, D. S., Geisbert, J. B., Scott, D. P., Kagan, E., Jahrling, P. B., Davis, K. J. (2003). Pathogenesis of Ebola Hemorrhagic Fever in Cynomolgus Macaques: Evidence that Dendritic Cells Are Early and Sustained Targets of Infection. Am. J. Pathol. 163: 2347-2370 [Abstract] [Full Text]
Probst, H. C., Tschannen, K., Gallimore, A., Martinic, M., Basler, M., Dumrese, T., Jones, E., van den Broek, M. F. (2003). Immunodominance of an Antiviral Cytotoxic T Cell Response Is Shaped by the Kinetics of Viral Protein Expression. J. Immunol. 171: 5415-5422 [Abstract] [Full Text]
Ontiveros, E., Kim, T. S., Gallagher, T. M., Perlman, S. (2003). Enhanced Virulence Mediated by the Murine Coronavirus, Mouse Hepatitis Virus Strain JHM, Is Associated with a Glycine at Residue 310 of the Spike Glycoprotein. J. Virol. 77: 10260-10269 [Abstract] [Full Text]
Morrow, G., Slobedman, B., Cunningham, A. L., Abendroth, A. (2003). Varicella-Zoster Virus Productively Infects Mature Dendritic Cells and Alters Their Immune Function. J. Virol. 77: 4950-4959 [Abstract] [Full Text]
Beyer, W. R., Popplau, D., Garten, W., von Laer, D., Lenz, O. (2003). Endoproteolytic Processing of the Lymphocytic Choriomeningitis Virus Glycoprotein by the Subtilase SKI-1/S1P. J. Virol. 77: 2866-2872 [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]
Grande-Perez, A., Sierra, S., Castro, M. G., Domingo, E., Lowenstein, P. R. (2002). From the Cover: Molecular indetermination in the transition to error catastrophe: Systematic elimination of lymphocytic choriomeningitis virus through mutagenesis does not correlate linearly with large increases in mutant spectrum complexity. Proc. Natl. Acad. Sci. USA 99: 12938-12943 [Abstract] [Full Text]
Junt, T., Nakano, H., Dumrese, T., Kakiuchi, T., Odermatt, B., Zinkernagel, R. M., Hengartner, H., Ludewig, B. (2002). Antiviral Immune Responses in the Absence of Organized Lymphoid T Cell Zones in plt/plt Mice. J. Immunol. 168: 6032-6040 [Abstract] [Full Text]
Spiropoulou, C. F., Kunz, S., Rollin, P. E., Campbell, K. P., Oldstone, M. B. A. (2002). New World Arenavirus Clade C, but Not Clade A and B Viruses, Utilizes {alpha}-Dystroglycan as Its Major Receptor. J. Virol. 76: 5140-5146 [Abstract] [Full Text]
Oldstone, M. B. A., Race, R., Thomas, D., Lewicki, H., Homann, D., Smelt, S., Holz, A., Koni, P., Lo, D., Chesebro, B., Flavell, R. (2002). Lymphotoxin-{alpha}- and Lymphotoxin-{beta}-Deficient Mice Differ in Susceptibility to Scrapie: Evidence against Dendritic Cell Involvement in Neuroinvasion. J. Virol. 76: 4357-4363 [Abstract] [Full Text]
Muller, S., Hunziker, L., Enzler, S., Buhler-Jungo, M., Di Santo, J. P., Zinkernagel, R. M., Mueller, C. (2002). Role of an Intact Splenic Microarchitecture in Early Lymphocytic Choriomeningitis Virus Production. J. Virol. 76: 2375-2383 [Abstract] [Full Text]
Dalod, M., Salazar-Mather, T. P., Malmgaard, L., Lewis, C., Asselin-Paturel, C., Briere, F., Trinchieri, G., Biron, C. A. (2002). Interferon {alpha}/{beta} and Interleukin 12 Responses to Viral Infections: Pathways Regulating Dendritic Cell Cytokine Expression In Vivo. JEM 195: 517-528 [Abstract] [Full Text]
Beyer, W. R., Westphal, M., Ostertag, W., von Laer, D. (2002). Oncoretrovirus and Lentivirus Vectors Pseudotyped with Lymphocytic Choriomeningitis Virus Glycoprotein: Generation, Concentration, and Broad Host Range. J. Virol. 76: 1488-1495 [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]
Ou, R., Zhou, S., Huang, L., Moskophidis, D. (2001). Critical Role for Alpha/Beta and Gamma Interferons in Persistence of Lymphocytic Choriomeningitis Virus by Clonal Exhaustion of Cytotoxic T Cells. J. Virol. 75: 8407-8423 [Abstract] [Full Text]
Ohgimoto, S., Ohgimoto, K., Niewiesk, S., Klagge, I. M., Pfeuffer, J., Johnston, I. C. D., Schneider-Schaulies, J., Weidmann, A., ter Meulen, V., Schneider-Schaulies, S. (2001). The haemagglutinin protein is an important determinant of measles virus tropism for dendritic cells in vitro. J. Gen. Virol. 82: 1835-1844 [Abstract] [Full Text]
Yamada, H., Saito, F., Fukuta-Ohi, H., Zhong, D., Hase, A., Arai, K., Okuyama, A., Maekawa, R., Shimizu, T., Matsumura, K. (2001). Processing of {beta}-dystroglycan by matrix metalloproteinase disrupts the link between the extracellular matrix and cell membrane via the dystroglycan complex. Hum Mol Genet 10: 1563-1569 [Abstract] [Full Text]
Arbour, N., Naniche, D., Homann, D., Davis, R. J., Flavell, R. A., Oldstone, M. B.A. (2002). c-Jun NH2-Terminal Kinase (JNK)1 and JNK2 Signaling Pathways Have Divergent Roles in CD8+ T Cell-mediated Antiviral Immunity. JEM 195: 801-810 [Abstract] [Full Text]
Kunz, S., Sevilla, N., McGavern, D. B., Campbell, K. P., Oldstone, M. B.A. (2001). Molecular analysis of the interaction of LCMV with its cellular receptor {alpha}-dystroglycan. JCB 155: 301-310 [Abstract] [Full Text]