Alpha-(1-3)- and alpha-(1-6)-D-mannose-specific plant lectins are markedly inhibitory to human immunodeficiency virus and cytomegalovirus infections in vitro.
The alpha-(1-3)-D-mannose- and alpha-(1-6)-D-mannose-specific agglutinins (lectins) from Galanthus nivalis, Hippeastrum hybrid, Narcissus pseudonarcissus, and Listera ovata inhibited infection of MT-4 cells by human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) and simian immunodeficiency virus at concentrations comparable to the concentrations at which dextran sulfate (molecular weight, 5,000 [DS-5000]) inhibits these viruses (50% effective concentration, 0.2 to 0.6 microgram/ml). Unlike DS-5000, however, the plant lectins did not inhibit the replication of other enveloped viruses, except for human cytomegalovirus (50% effective concentration, 0.9 to 1.6 microgram/ml). The plant lectins suppressed syncytium formation between persistently HIV-1- or HIV-2-infected HUT-78 cells and uninfected MOLT-4 (clone 8) cells at concentrations that were 5- to 10-fold lower than that required for DS-5000. Unlike DS-5000, however, the plant lectins did not inhibit HIV-1 binding to CD4+ cells. Combination of the plant lectins with DS-5000 led to a potent synergistic inhibition of HIV-1-induced cytopathogenicity in MT-4 cells and syncytium formation between HIV-infected HUT-78 cells and MOLT-4 cells. Our data suggest that alpha-(1-3)-D- and alpha-(1-6)-D-mannose-specific plant lectins interfere with an event in the HIV replicative cycle that is subsequent to the attachment of the virions to the cells (i.e., the fusion process).
Balzarini
J
J
Laboratory of Chemotherapy, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
Schols
D
D
Neyts
J
J
Van Damme
E
E
Peumans
W
W
De Clercq
E
E
D000911:Antibodies, Monoclonal / Q000378:metabolism; D000998:Antiviral Agents / Q000494:pharmacology*; D015704:CD4 Antigens / Q000276:immunology; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000187:drug effects* / Q000378:metabolism; D027801:Galanthus; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D037102:Lectins / Q000494:pharmacology*; D008358:Mannose / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology; D037121:Plant Lectins; D015302:Simian Immunodeficiency Virus / Q000187:drug effects* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D015704:CD4 Antigens; D037102:Lectins; D010936:Plant Extracts; D037121:Plant Lectins; D008358:Mannose