The Journal of Experimental Medicine
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Published online 6 November 2000.
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© 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 Sevillaa, Stefan Kunza, Andreas Holza, Hanna Lewickia, Dirk Homanna, Hiroki Yamadab, Kevin P. Campbellb, Juan C. de la Torrea, and Michael B.A. Oldstonea

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
Division of Virology, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037.858-784 9981858-784 8054

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.

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

Abbreviations used in this paper: aa, amino acid(s); APC, allophycocyanin; ARM, Armstrong; BHK, baby hamster kidney; CNS, central nervous system; Cl, clone; DC, dendritic cell; {alpha}-DG, {alpha}-dystroglycan; ECM, extracellular matrix; GP, glycoprotein; IDC, interdigitating dendritic cell; IS, immunosuppression phenotype; ko, knockout; LCMV, lymphocytic choriomeningitis virus; NP, nucleoprotein; P, persistence phenotype; RT, reverse transcriptase; S, small; VOPBA, virus overlay protein binding assay.

© 2000 The Rockefeller University Press


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