Capture and transmission of HIV-1 by the C-type lectin L-SIGN (DC-SIGNR) is  inhibited by carbohydrate-binding agents and polyanions.
It was recently shown that capture of HIV-1 by DC-SIGN-expressing cells and the subsequent transmission of HIV to CD4+ T-lymphocytes can be prevented by carbohydrate-binding agents (CBAs), whereas polyanions were unable to block virus capture by DC-SIGN. In this study, we could show that a short pre-exposure of HIV-1 to both mannose- and N-acetylglucosamine (GlcNAc)-specific CBAs or polyanions dose-dependently prevented virus capture by L-SIGN-expressing 293T-REx/L-SIGN cells and subsequent syncytia formation in co-cultures of the drug-exposed HIV-1-captured 293T-REx/L-SIGN cells and uninfected C8166 CD4+ T-lymphocytes. Additionally, the inhibitory potential of the compounds against L-SIGN-mediated HIV-1 capture and transmission was more pronounced than observed for DC-SIGN expressing293T-REx/DC-SIGN cells. The excess value of CBAs and polyanions to prevent HIV-1 capture and transmission by DC-SIGN and L-SIGN-expressing cells to susceptible T-lymphocytes could be of interest for the development of new drug leads targeting HIV entry/fusion.
Auwerx
Joeri
J
Virology and Chemotherapy, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium.
François
Katrien O
KO
Vanstreels
Els
E
Van Laethem
Kristel
K
Daelemans
Dirk
D
Schols
Dominique
D
Balzarini
Jan
J
D019380:Anti-HIV Agents / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D037102:Lectins / Q000494:pharmacology*; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors*; D000071228:Polyelectrolytes; D011108:Polymers / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors*; D053585:Virus Attachment / Q000187:drug effects*
D019380:Anti-HIV Agents; D015815:Cell Adhesion Molecules; D037102:Lectins; D037181:Lectins, C-Type; D000071228:Polyelectrolytes; D011108:Polymers; D011956:Receptors, Cell Surface; C433029:CLEC4M protein, human