Journal article
Differences in Affinity of Binding of Lymphocytic Choriomeningitis Virus Strains to the Cellular Receptor α-Dystroglycan Correlate with Viral Tropism and Disease Kinetics
Journal of virology, Vol.75(1), pp.448-457
01/2001
DOI: 10.1128/JVI.75.1.448-457.2001
PMCID: PMC113937
PMID: 11119613
Abstract
α-Dystroglycan (α-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 α-DG determines viral tropism and the outcome of infection in mice. To characterize this relationship, we evaluated the interaction between α-DG and several LCMV strains, variants, and reassortants. These viruses could be divided into two groups with respect to affinity of binding to α-DG, dependence on this protein for cell entry, viral tropism, and disease course. Viruses that exhibited high-affinity binding to α-DG displayed a marked dependence on α-DG for cell entry and were blocked from infecting mouse 3T6 fibroblasts by 1 to 4 nM soluble α-DG. In addition, high-affinity binding to α-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 α-DG were only partially inhibited from infecting α-DG
−/−
embryonic stem cells and required a concentration of soluble α-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 α-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.
Details
- Title: Subtitle
- Differences in Affinity of Binding of Lymphocytic Choriomeningitis Virus Strains to the Cellular Receptor α-Dystroglycan Correlate with Viral Tropism and Disease Kinetics
- Creators
- Sara C Smelt - Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037Persephone Borrow - Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037Stefan Kunz - Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037Wei Cao - Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037Antoinette Tishon - Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037Hanna Lewicki - Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037Kevin P Campbell - Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037Michael B. A Oldstone - Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.75(1), pp.448-457
- Publisher
- American Society for Microbiology
- DOI
- 10.1128/JVI.75.1.448-457.2001
- PMID
- 11119613
- PMCID
- PMC113937
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Language
- English
- Date published
- 01/2001
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9984020864902771
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