A comparative study of the effect of dextran sulfate on the fusion and the in vitro replication of influenza A and B, Semliki Forest, vesicular stomatitis, rabies, Sendai, and mumps virus

Abstract

The effect of dextran sulfate on the fusion of a series of enveloped viruses, bearing specifically different fusion proteins, was investigated. The fusion with model- and with biological membranes was monitored by an R18 fluorescence-dequenching fusion assay. Dextran sulfate strongly suppresses the fusion of orthomxyo- (influenza A (H1N1 and H3N2 subtypes) and influenza B), of toga- (Semliki Forest virus), and of rhabdoviruses (vesicular stomatitis and rabies virus). The fusion of the paramyxo-viruses Sendai and mumps was not significantly affected by the anionic polysaccharide. The response to dextran sulfate was virus-specific, and identical for the different members of one virusfamily, bearing the same fusion protein. It was shown that dextran sulfate attaches with high affinity to the viruses studied, but not to erythrocytes. The anionic polymer appears to attach to the fusion epitope of the viral membrane. The inhibition of virus replication in vitro shows a remarkable correlation with the observed anti-fusion effects of dextran sulfate.

Dextran sulfate-resistant A/Puerto Rico/8/34 influenza virus is associated with the emergence of specific mutations in the neuraminidase glycoprotein

“…However, there are few studies on the role of the negative electric charge of DS in the DS-dependent suppression of influenza virus replication. DS was previously shown by direct binding experiments with FITC-labeled DS to bind to the viral membrane glycoproteins of influenza viruses (Lüscher-Mattli et al, 1993). We previously showed that the suppression of PR8 viral replication by DS was neutralized dose-dependently by adding diethylaminoethyl-dextran, a positively charged dextran (Yamada et al, 2012).…”

“…They also suggested that another binding site within the pocket formed by the 430-loop could be accessed by the new inhibitors. Novel antiviral compounds were identified which targeted the catalytic cavity as well as the 150-and 430-loops and which exhibit dynamic properties in electrostatic surface and geometric shape (Cheng et al, (De Clercq, 1986;Baba et al, 1988;Lüscher-Mattli et al, 1993). Some reports indicate that the negative charge of DS is associated with this inhibition.…”

“…In particular, DS inhibits the replication of human immunodeficiency virus (HIV), herpes simplex virus and vesicular stomatitis virus by suppressing virus adsorption to cell membranes or the virus-cellular membrane fusion process (De Clercq, 1986;Mitsuya et al, 1988;Baba et al, 1988;Lüscher-Mattli et al, 1993). These viruses reportedly use negatively charged cell-membrane components such as sialic acid and heparan sulfate as cellular receptors, which they bind with positively charged ligands.…”

“…Besides the viruses listed above, DS has been reported to inhibit the replication of influenza A viruses (H1N1 and H3N2 subtypes), by suppressing the fusion process by viral hemagglutinin (HA) (Hosoya et al, 1991;Lüscher-Mattli et al, 1993). HA and NA are the two major surface glycoproteins of the influenza viral membrane.…”

Detection of Cell-Cell Fusion Mediated by Ebola Virus Glycoproteins

“…These experiments indicate that proteins on the target cell surface are required both for cell-cell fusion and for pseudotype infection mediated by EboV GP. Similarly, incubation of HeLa-P4 target cells with dextran sulfate (100 or 500 g/ml; 120 min), a glucidic macromolecule interacting with glycosaminoglycans and inhibiting infection by various types of viruses (18,22), resulted in decreased efficiency of fusion with cells expressing EboV GP (Fig. 4A).…”