title: Interactions of LSECtin and DC-SIGN/DC-SIGNR with viral ligands: Differential pH dependence, internalization and virion binding.
abstract: The calcium-dependent lectins DC-SIGN and DC-SIGNR (collectively termed DC-SIGN/R) bind to high-mannose carbohydrates on a variety of viruses. In contrast, the related lectin LSECtin does not recognize mannose-rich glycans and interacts with a more restricted spectrum of viruses. Here, we analyzed whether these lectins differ in their mode of ligand engagement. LSECtin and DC-SIGNR, which we found to be co-expressed by liver, lymph node and bone marrow sinusoidal endothelial cells, bound to soluble Ebola virus glycoprotein (EBOV-GP) with comparable affinities. Similarly, LSECtin, DC-SIGN and the Langerhans cell-specific lectin Langerin readily bound to soluble human immunodeficiency virus type-1 (HIV-1) GP. However, only DC-SIGN captured HIV-1 particles, indicating that binding to soluble GP is not necessarily predictive of binding to virion-associated GP. Capture of EBOV-GP by LSECtin triggered ligand internalization, suggesting that LSECtin like DC-SIGN might function as an antigen uptake receptor. However, the intracellular fate of lectin-ligand complexes might differ. Thus, exposure to low-pH medium, which mimics the acidic luminal environment in endosomes/lysosomes, released ligand bound to DC-SIGN/R but had no effect on LSECtin interactions with ligand. Our results reveal important differences between pathogen capture by DC-SIGN/R and LSECtin and hint towards different biological functions of these lectins.
authors: Institute of Virology, University Hospital Erlangen, 91054 Erlangen, Germany.
authors: Thomas
authors: T
authors: Gramberg
authors: Elizabeth
authors: E
authors: Soilleux
authors: Tanja
authors: T
authors: Fisch
authors: Patricia F
authors: PF
authors: Lalor
authors: Heike
authors: H
authors: Hofmann
authors: Sophie
authors: S
authors: Wheeldon
authors: Andrew
authors: A
authors: Cotterill
authors: Anja
authors: A
authors: Wegele
authors: Thomas
authors: T
authors: Winkler
authors: David H
authors: DH
authors: Adams
authors: Stefan
authors: S
authors: Pöhlmann
mesh_terms: D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D029043:Ebolavirus / Q000378:metabolism / Q000472:pathogenicity; D042783:Endothelial Cells / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism / Q000472:pathogenicity; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D037181:Lectins, C-Type / Q000378:metabolism*; D008024:Ligands; D010957:Plasmids / Q000235:genetics; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*; D014771:Virion / Q000378:metabolism; D053586:Virus Internalization; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D008024:Ligands; D011956:Receptors, Cell Surface; D014759:Viral Envelope Proteins; D054299:env Gene Products, Human Immunodeficiency Virus; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C505228:CLEC4G protein, human; C433029:CLEC4M protein, human; C113189:envelope glycoprotein, Ebola virus