Activation of the lectin DC-SIGN induces an immature dendritic cell phenotype triggering Rho-GTPase activity required for HIV-1 replication.

Ashleigh Hodges (1) , Katherine Sharrocks (1) , Mariola Edelmann (2) , Dilair Baban (3) , Arnaud Moris (4) , Olivier Schwartz (4) , Hal Drakesmith (1) , Kay E. Davies (3) , Benedikt Kessler (2) , Andrew J. Mcmichael (1) , Alison Simmons (1)

1 MRC Human Immunology Unit
2 The Henry Wellcome Building for Molecular Physiology
3 Medical Research Council Functional Genetics Unit
4 Virus et Immunité

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.

Domains: Immunology

Ashleigh Hodges, Katherine Sharrocks, Mariola Edelmann, Dilair Baban, Arnaud Moris, et al.. Activation of the lectin DC-SIGN induces an immature dendritic cell phenotype triggering Rho-GTPase activity required for HIV-1 replication.. Nature Immunology, 2007, 8 (6), pp.569-77. ⟨10.1038/ni1470⟩. ⟨pasteur-00292841⟩