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(+) 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.
Sevilla
N
N
Department of Neuropharmacology, Division of Virology, The Scripps Research Institute, La Jolla, California 92037, USA.
Kunz
S
S
Holz
A
A
Lewicki
H
H
Homann
D
D
Yamada
H
H
Campbell
K P
KP
de La Torre
J C
JC
Oldstone
M B
MB
D000818:Animals; D015703:Antigens, CD; D018845:CD11 Antigens / Q000276:immunology; D002460:Cell Line; D002490:Central Nervous System / Q000821:virology; D002908:Chronic Disease; D006224:Cricetinae; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D049030:Dystroglycans; D007165:Immunosuppression Therapy; D017403:In Situ Hybridization; D037181:Lectins, C-Type; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000032:analysis / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D015778:Minor Histocompatibility Antigens; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000032:analysis; D011991:Receptors, Virus / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000502:physiology; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
D015703:Antigens, CD; D018845:CD11 Antigens; D003598:Cytoskeletal Proteins; C093569:DEC-205 receptor; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins; D049030:Dystroglycans