Journal
NATURE IMMUNOLOGY
Volume 8, Issue 6, Pages 569-577Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni1470
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Funding
- Medical Research Council [MC_U137761449, MC_U137884177] Funding Source: researchfish
- Medical Research Council [MC_U137761449, MC_U137884177] Funding Source: Medline
- MRC [MC_U137761449, MC_U137884177] Funding Source: UKRI
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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.
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