Capture and transmission of HIV-1 by the C-type lectin L-SIGN (DC-SIGNR) is inhibited by carbohydrate-binding agents and polyanions

• Published in: Antiviral research 2009-07, Vol.83 (1), p.61-70
• Main Authors: Auwerx, Joeri, François, Katrien O., Vanstreels, Els, Van Laethem, Kristel, Daelemans, Dirk, Schols, Dominique, Balzarini, Jan
• Format: Article
• Language: English
• Subjects: Anti-HIV Agents - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Carbohydrate-binding agents (CBA); CD4-Positive T-Lymphocytes - virology; Cell Adhesion Molecules - antagonists & inhibitors; Cell Line; DC-SIGN; Dose-Response Relationship, Drug; HIV; HIV-1 - drug effects; HIV-1 - physiology; Human immunodeficiency virus 1; Human viral diseases; Humans; Infectious diseases; L-SIGN; Lectins - pharmacology; Lectins, C-Type - antagonists & inhibitors; Medical sciences; Pharmacology. Drug treatments; Polyanions; Polymers - pharmacology; Receptors, Cell Surface - antagonists & inhibitors; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Virus Attachment - drug effects; Virus transmission
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2009.03.011

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-expressing 293T-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.