Enhancement of human parainfluenza virus-induced cell fusion by pradimicin, a low molecular weight mannose-binding antibiotic

Abstract

Oligosaccharides, especially mannose residues, expressed on the cell surface, are thought to be important for virus-induced membrane fusion. We examined the effect of mannose-binding compounds, pradimicin derivative BMY-28,864 (PRM) and concanavalin A (Con A), on cell fusion of human parainfluenza type 2 virus (hPIV2)-infected HeLa cells. Syncytium formation of hPIV2-infected HeLa cells was suppressed in the presence of Con A. On the other hand, PRM enhanced cell fusion of hPIV2-infected HeLa cells. These effects were blocked by addition of mannose-rich mannan. However, PRM shows little effect on virus growth and the expression of viral glycoproteins on the cell surface in hPIV2-infected HeLa cells. Fluorescein-isothiocyanate-labeled pradimicin and Con A bound to both uninfected and hPIV2-infected mononuclear cells, indicating that these compounds have an affinity to several cellular component(s). In contrast to Con A, PRM had little affinity to the viral glycoproteins. It is inferred from these results that the enhancement of hPIV2-induced cell fusion is probably due to the interaction between PRM and cellular component(s).

The carbohydrate-binding plant lectins and the non-peptidic antibiotic pradimicin A target the glycans of the coronavirus envelope glycoproteins

“…This surprising result might be explained by a tethering effect of CBA, which might facilitate virus -cell attachment and subsequently productive infection. 47 Indeed, the CBA evaluated in this study are able to bind multiple carbohydrate moieties. 11,12 The role of host cells in determining the sensitivity to CBA was underscored by the observed altered sensitivity of genetically identical viruses, which were propagated on different cell lines.…”

The effect of concanavalin A on the replication of rotavirus (SA-11) in cell culture

“…Therefore, the highly specific interaction of lectins with sugars would point out for the possibility of positive or negative modulation of virus binding to host cells. As previously described, lectins have been used as valuable tool for monitoring virus (Becht et al, 1972;Okada & Kim, 1972;Ito & Barron, 1974;Poste et al, 1974;Cartwright, 1977;Takehara, 1979;Khélifa & Menezes, 1982;Conti & Tsiang, 1985;Okamoto et al, 1997). On the other hand, a few data are available concerning the effect of ConA on the replication of nonenveloped viruses (Okada & Kim, 1972;Ito & Barron, 1974;Lonberg-Holm, 1975 Kopecky et al, 1991;Okamoto et al, 1997).…”

“…Concanavalin A (ConA), a lectin from jack bean, binds specifically to mannosyl and glycosyl residues. This lectin has been extensively used for the study of virus attachment to host cells and characterization of glycoproteins involved, mainly concerned to the enveloped viruses (Calafat & Hageman, 1972;Okada & Kim, 1972;Miki, 1980;Conti & Tsiang, 1985;Grail & Norval, 1986;Kopecky et al, 1991;Okamoto et al, 1997). Svensson (1984) demonstrated that RV express mannosyl residues in VP7.…”