Abstract
Among cells of the immune system, CD11c(+) and DEC-205(+) splenic dendritic 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 affinity are associated with virus replication in the white pulp, show preferential 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 affinity to alpha-DG are associated with viral replication in the red pulp, display minimal replication in CD11c(+) and DEC-205(+) cells, and generate a robust anti-LCMV cytotoxic T lymphocyte response that clears the virus infection. Differences in binding affinities can be mapped to a single amino acid change in the viral glycoprotein 1 ligand that binds to alpha-DG. These findings indicate that receptor-virus interaction on dendritic cells in vivo can be an essential step in the initiation of virus-induced immunosuppression and viral persistence.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigens, CD*
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CD11 Antigens / immunology
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Cell Line
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Central Nervous System / virology
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Chronic Disease
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Cricetinae
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Cytoskeletal Proteins / metabolism
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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Dendritic Cells / virology*
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Dystroglycans
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Immunosuppression Therapy*
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In Situ Hybridization
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Lectins, C-Type*
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Lymphocytic Choriomeningitis / immunology
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Lymphocytic Choriomeningitis / virology
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Lymphocytic choriomeningitis virus / genetics
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Lymphocytic choriomeningitis virus / immunology
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Lymphocytic choriomeningitis virus / isolation & purification
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Lymphocytic choriomeningitis virus / physiology*
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Membrane Glycoproteins / analysis
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Membrane Glycoproteins / metabolism
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Mice
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Mice, Inbred BALB C
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Mice, Knockout
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Minor Histocompatibility Antigens
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Protein Binding
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Receptors, Cell Surface / analysis
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Receptors, Virus / metabolism
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Spleen / cytology
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Spleen / immunology
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Spleen / virology
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T-Lymphocytes, Cytotoxic / immunology
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / physiology
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Viral Proteins / genetics
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Viral Proteins / metabolism
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Virus Replication
Substances
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Antigens, CD
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CD11 Antigens
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Cytoskeletal Proteins
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DEC-205 receptor
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Lectins, C-Type
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Membrane Glycoproteins
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Minor Histocompatibility Antigens
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Receptors, Cell Surface
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Receptors, Virus
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Tumor Necrosis Factor-alpha
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Viral Proteins
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Dystroglycans