Alpha-(1-3)- and alpha-(1-6)-D-mannose-specific plant lectins are markedly inhibitory to human immunodeficiency virus and cytomegalovirus infections in vitro

Abstract

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).

Characterization and molecular cloning of mannose‐binding lectins from the Orchidaceae species Listera ovata, Epipactis helleborine and Cymbidium hybrid

“…Like Amaryllidaceae, onion and leek lectins, the orchid lectins were also shown to be very potent inhibitors of the infection of target cells by some human and animal retroviruses (Balzarini et al, 1991(Balzarini et al, , 1992. Using double-immunodiffusion assays it was shown that the orchid lectins isolated from L. ovata, E. helleborine and Cymbidium hybrid also react with antibodies raised against the snowdrop lectin and cross react with the G. nivalis lectin, indicating that these Orchidaceae lectins are serologically related to the snowdrop lectin.…”

“…Since all orchid lectins strongly resemble each other with respect to their molecular structure and carbohydrate-binding specificity, and also strongly resemble the previously isolated Amaryllidaceae lectins in terms of molecular structure and antiviral properties (Balzarini et al, 1991(Balzarini et al, , 1992, it seemed worthwhile to examine a possible serological relationship between these lectins. Polyclonal antisera prepared against the L. ovata lectin and the G. nivalis lectin were challenged with the different orchid lectins and the snowdrop lectin.…”

“…Due to its high specificity for mannans, the L. ovata lectin is of great utility for the separation of amannans from a-glucans, and for investigating the structure of complex carbohydrates, especially those possessing al,3-mannosidic linkages (Saito et al, 1993). Like the Amaryllidaceae lectins and the onion and leek lectins (Balzarini et al, 1991(Balzarini et al, , 1992, the L. ovata lectin was also shown to be a potent inhibitor of the infection of target cells by some human and animal retroviruses (Balzarini et al, 1991) which makes this lectin a useful tool in acquired-immunodeficiency-syndrome research.…”

Envelope glycans of immunodeficiency virions are almost entirely oligomannose antigens

“…2A). Moreover, the prevalence of Man 5 GlcNAc 2 compared with recombinant envelope may explain the surprising antiviral efficacy of lectins to Manα1→3 and Manα1→6 terminating glycans (39). Furthermore, as the most conserved and abundant glycan structure on the viral envelope, Man 5 GlcNAc 2 should itself be evaluated as a target for vaccine design.…”

Directing the Immune Response to Carbohydrate Antigens

“…Lectins are also particularly relevant to human immunodeficiency virus (HIV) pathogenesis. Lectin-induced inhibition of syncytium formation and infection of cells by both T-cell line adapted and primary isolates (21)(22)(23)(24)(25)(26)(27) focuses attention on oligomannosidic glycans, such as those characterized by interaction with ConA ( Fig. 1).…”