Antiviral activity of carbohydrate-binding agents and the role of DC-SIGN in dengue virus infection.
Dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) is an important binding receptor for dengue virus (DENV) that recognizes N-glycosylation sites on the viral E-glycoprotein. DENV cannot bind nor infect the human B-cell line Raji/0. However, DENV productively infects Raji/DC-SIGN(+) cells that constitutively express DC-SIGN on their surface. IL-4-treated monocytes, expressing high levels of DC-SIGN, are also susceptible for DENV infection. Several carbohydrate-binding agents (CBAs), such as the plant lectins HHA, GNA (mannose-specific) and UDA (N-acetylglucosamine-specific), inhibited dose-dependently the binding of DENV and subsequently viral replication in Raji/DC-SIGN(+) cells (EC(50): 0.1-2.2 microM). These CBAs were clearly more active against DENV in IL-4-treated monocytes (EC(50): 4-56 nM). However, the CBAs were devoid of antiviral activity in DENV-susceptible Vero-B (DC-SIGN(-)) cells, demonstrating cell type-dependent differences in viral entry mechanisms.
Alen
Marijke M F
MM
Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
Kaptein
Suzanne J F
SJ
De Burghgraeve
Tine
T
Balzarini
Jan
J
Neyts
Johan
J
Schols
Dominique
D
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002522:Chlorocebus aethiops; D003715:Dengue / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D003716:Dengue Virus / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000821:virology; D037121:Plant Lectins / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014709:Vero Cells; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D000998:Antiviral Agents; D015815:Cell Adhesion Molecules; D015847:Interleukin-4; D037181:Lectins, C-Type; D037121:Plant Lectins; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin