The C Type Lectins DC-SIGN and L-SIGN

Abstract

DC-SIGN and L-SIGN are C-type lectins that recognize carbohydrate structures present on viral glycoproteins and function as attachment factors for several enveloped viruses. DC-SIGN and L-SIGN enhance viral entry and facilitate infection of cells that express the cognate entry receptor (cis-infection). They are also able to capture viruses and transfer viral infections to other target cells (trans-infection). In this chapter, we will give an overview of protocols used to produce soluble viral glycoproteins at high levels and to study the molecular basis of viruses/DC-SIGN and L-SIGN binding and internalization. We will also describe techniques to investigate the molecular mechanisms by which DC-SIGN or L-SIGN spread viral infections.

Myeloid C-Type Lectin Receptors in Viral Recognition and Antiviral Immunity

“…As DC-SIGN, L-SIGN is a type II transmembrane protein with a short cytoplasmic tail involved in signaling and internalization, a transmembrane region, a neck domain consisting of eight repeat regions of 23 amino acids, and a Ca 2+ -dependent CRD [63]. Oppositely to DC-SIGN, L-SIGN presents a highly variable and polymorphic neck region, which impacts ligand-binding affinity and specificity for viral pathogens [40,44].…”

“…The neck region of L-SIGN is essential for tetramerization, thus increasing the binding avidity to multivalent ligands displayed on pathogen surfaces [44]. L-SIGN expression is restricted to endothelial cells present in lymph nodes, placenta, and liver sinusoidal endothelial cells [63]. L-SIGN binds to N -linked high-mannose oligosaccharides, with a binding preference for mannosylated residues [44].…”

Pseudotyping Lentiviral Vectors with Aura Virus Envelope Glycoproteins for DC-SIGN–Mediated Transduction of Dendritic Cells

“…4A,B). These treatments disrupt interactions with DC-SIGN molecules (Klimstra et al, 2003;Davis et al, 2006;Lozach et al, 2007). Incubation with mannan, a natural ligand for DC-SIGN, during viral inoculation of FUGW/AURAG and FUGW/SING with 293T.DCSIGN cells resulted in a dose-dependent reduction in the amount of GFP-positive cells (Fig.…”

Hepatitis C virus and proprotein convertase subtilisin/kexin type 9: a detrimental interaction to increase viral infectivity and disrupt lipid metabolism

“…E1 and E2 glycoproteins, which serve as the fusogenic subunits during the process of HCV entry, are believed to function as HCV capture receptors 12. In addition, E1 and E2 interact with the CD81 tetraspanin and lipoprotein receptors; this interaction allows the transfer of the virus from the surface to side gradually.…”

“…In the ER and Golgi apparatus, viral envelope acquisition and maturation occur through a molecular pathway overlapping with lipoprotein secretion 9. The mature virions may be then released into circulation as lipoprotein‐like particles, named lipo‐viro‐particles (LVP), which contain different hepatocyte‐synthesized apolipoproteins 8, 10, 11, 12. It is believed that LVP particle‐associated apolipoproteins may increase viral infectivity, participate in lipoprotein receptor‐mediated viral entry and have a crucial role for intracellular maturation of HCV particles.…”