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DC-SIGN, a C-type lectin expressed on dendritic cells (DCs), can sequester human immunodeficiency virus (HIV) virions in multivesicular bodies. Here, using large-scale gene expression profiling and tyrosine-phosphorylated proteome analyses, we characterized signaling mediated by DC-SIGN after activation by either HIV or a DC-SIGN-specific antibody. Activation of DC-SIGN resulted in downregulation of genes encoding major histocompatibility complex class II, Jagged 1 and interferon-response molecules and upregulation of the gene encoding transcription factor ATF3. Phosphorylated proteome analysis showed that HIV- or antibody-stimulated DC-SIGN signaling was mediated by the Rho guanine nucleotide-exchange factor LARG and led to increased Rho-GTPase activity. Activation of LARG in DCs exposed to HIV was required for the formation of virus-T cell synapses. Thus, HIV sequestration by and stimulation of DC-SIGN helps HIV evade immune responses and spread to cells.

Original publication

DOI

10.1038/ni1470

Type

Journal article

Journal

Nat Immunol

Publication Date

06/2007

Volume

8

Pages

569 - 577

Keywords

Amino Acid Sequence, Cell Adhesion Molecules, Cell Differentiation, Cells, Cultured, Dendritic Cells, Enzyme Activation, Gene Expression Profiling, Guanine Nucleotide Exchange Factors, HIV-1, Humans, Lectins, C-Type, Molecular Sequence Data, Phenotype, Phosphoserine, Receptors, Cell Surface, Rho Guanine Nucleotide Exchange Factors, Signal Transduction, T-Lymphocytes, Transcription, Genetic, Virus Replication, rho GTP-Binding Proteins