This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Smelt, S. C. Articles by Oldstone, M. B. A. Search for Related Content PubMed PubMed Citation Articles by Smelt, S. C. Articles by Oldstone, M. B. A.

Journal of Virology, January 2001, p. 448-457, Vol. 75, No. 1
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.1.448-457.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Differences in Affinity of Binding of Lymphocytic Choriomeningitis Virus Strains to the Cellular Receptor -Dystroglycan Correlate with Viral Tropism and Disease Kinetics

Sara C. Smelt,^1,* Persephone Borrow,² Stefan Kunz,¹ Wei Cao,³ Antoinette Tishon,¹ Hanna Lewicki,¹ Kevin P. Campbell,⁴ and Michael B. A. Oldstone¹

Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037¹; The Edward Jenner Institute for Vaccine Research, Compton, Newbury, Berkshire RG20 7NN, United Kingdom²; Aviron, Mountain View, California 94034³; and Howard Hughes Medical Institute, Departments of Physiology, Biophysics, and Neurology, University of Iowa College of Medicine, Iowa City, Iowa 52242⁴

Received 14 July 2000/Accepted 2 October 2000

-Dystroglycan (-DG) was recently identified as a receptor for lymphocytic choriomeningitis virus (LCMV) and several other arenaviruses, including Lassa fever virus (W. Cao, M. D. Henry, P. Borrow, H. Yamada, J. H. Elder, E. V. Ravkov, S. T. Nichol, R. W. Compans, K. P. Campbell, and M. B. A. Oldstone, Science 282:2079-2081, 1998). Data presented in this paper indicate that the affinity of binding of LCMV to -DG determines viral tropism and the outcome of infection in mice. To characterize this relationship, we evaluated the interaction between -DG and several LCMV strains, variants, and reassortants. These viruses could be divided into two groups with respect to affinity of binding to -DG, dependence on this protein for cell entry, viral tropism, and disease course. Viruses that exhibited high-affinity binding to -DG displayed a marked dependence on -DG for cell entry and were blocked from infecting mouse 3T6 fibroblasts by 1 to 4 nM soluble -DG. In addition, high-affinity binding to -DG correlated with an ability to infiltrate the white pulp (T-dependent) area of the spleen, cause ablation of the cytotoxic T-lymphocyte (CTL) response by day 7 postinfection, and establish a persistent infection. In contrast, viruses with a lower affinity of binding to -DG were only partially inhibited from infecting -DG^/ embryonic stem cells and required a concentration of soluble -DG higher than 100 nM to prevent infection of mouse 3T6 fibroblasts. These viruses that bound at low affinity were mainly restricted to the splenic red pulp, and the host generated an effective CTL response that rapidly cleared the infection. Reassortants of viruses that bound to -DG at high and low affinities were used to map genes responsible for the differences described to the S RNA, containing the virus attachment protein glycoprotein 1.

---

^* Corresponding author. Mailing address: Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037. Phone: (858) 784-8737. Fax: (858) 784-9981. E-mail: ssmelt{at}scripps.edu.

Manuscript 13229-NP of the Scripps Research Institute.

---

Journal of Virology, January 2001, p. 448-457, Vol. 75, No. 1
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.1.448-457.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

This article has been cited by other articles:

• Dylla, D. E., Michele, D. E., Campbell, K. P., McCray, P. B. Jr. (2008). Basolateral Entry and Release of New and Old World Arenaviruses from Human Airway Epithelia. J. Virol. 82: 6034-6038 [Abstract] [Full Text]  
• Flanagan, M. L., Oldenburg, J., Reignier, T., Holt, N., Hamilton, G. A., Martin, V. K., Cannon, P. M. (2008). New World Clade B Arenaviruses Can Use Transferrin Receptor 1 (TfR1)-Dependent and -Independent Entry Pathways, and Glycoproteins from Human Pathogenic Strains Are Associated with the Use of TfR1. J. Virol. 82: 938-948 [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]  
• Mothe, B. R., Stewart, B. S., Oseroff, C., Bui, H.-H., Stogiera, S., Garcia, Z., Dow, C., Rodriguez-Carreno, M. P., Kotturi, M., Pasquetto, V., Botten, J., Crotty, S., Janssen, E., Buchmeier, M. J., Sette, A. (2007). Chronic Lymphocytic Choriomeningitis Virus Infection Actively Down-Regulates CD4+ T Cell Responses Directed against a Broad Range of Epitopes. J. Immunol. 179: 1058-1067 [Abstract] [Full Text]  
• Guglielmi, K. M., Kirchner, E., Holm, G. H., Stehle, T., Dermody, T. S. (2007). Reovirus Binding Determinants in Junctional Adhesion Molecule-A. J. Biol. Chem. 282: 17930-17940 [Abstract] [Full Text]  
• Rojek, J. M., Spiropoulou, C. F., Campbell, K. P., Kunz, S. (2007). Old World and Clade C New World Arenaviruses Mimic the Molecular Mechanism of Receptor Recognition Used by {alpha}-Dystroglycan's Host-Derived Ligands. J. Virol. 81: 5685-5695 [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]  
• Sanchez, A. B., de la Torre, J. C. (2005). Genetic and Biochemical Evidence for an Oligomeric Structure of the Functional L Polymerase of the Prototypic Arenavirus Lymphocytic Choriomeningitis Virus. J. Virol. 79: 7262-7268 [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]  
• 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]  
• 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]  
• Flodstrom, M., Tsai, D., Fine, C., Maday, A., Sarvetnick, N. (2003). Diabetogenic Potential of Human Pathogens Uncovered in Experimentally Permissive {beta}-Cells. Diabetes 52: 2025-2034 [Abstract] [Full Text]  
• Badovinac, V. P., Nordyke Messingham, K. A., Hamilton, S. E., Harty, J. T. (2003). Regulation of CD8+ T Cells Undergoing Primary and Secondary Responses to Infection in the Same Host. J. Immunol. 170: 4933-4942 [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]  
• 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]  
• Malmgaard, L., Salazar-Mather, T. P., Lewis, C. A., Biron, C. A. (2002). Promotion of Alpha/Beta Interferon Induction during In Vivo Viral Infection through Alpha/Beta Interferon Receptor/STAT1 System-Dependent and -Independent Pathways. J. Virol. 76: 4520-4525 [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]  
• 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]  
• 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. J. Cell Biol. 155: 301-310 [Abstract] [Full Text]