Immunosuppression and resultant viral persistence by specific viral targeting of dendritic cells

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(+) calls, 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.