chondroitin-sulfates and Herpes-Simplex

The sulphated polysaccharide from the widespread Tridax procumbens plant was studied for the anticoagulant, antiherpetic and antibacterial activity. The anticoagulant activity was determined by the activated partial thromboplastin time assay. The sulphated polysaccharide from T. procumbens represented potent anticoagulant reaching the efficacy to heparin and chondroitin sulphate. Moreover, the sulphated polysaccharide extracted from T. procumbens was found non-toxic on Vero cell lines up to the concentration of 200 μg/ml. Sulphated polysaccharide exhibited detectable antiviral effect towards HSV-1 with IC(50) value 100-150 μg/ml. Furthermore, sulphated polysaccharide from T. procumbens was highly inhibitory against the bacterial strains Vibrio alginolyticus and Vibrio harveyi isolated from oil sardine.

Topics: Animals; Anti-Bacterial Agents; Anticoagulants; Antiviral Agents; Asteraceae; Chemistry, Pharmaceutical; Chlorocebus aethiops; Chondroitin Sulfates; Hemorrhage; Heparin; Herpes Simplex; Herpesvirus 1, Human; Inhibitory Concentration 50; Partial Thromboplastin Time; Phytotherapy; Plant Extracts; Plants, Medicinal; Polysaccharides; Vero Cells; Vibrio alginolyticus; Vibrio Infections

The role of glycoprotein C (gC) for binding of herpes simplex virus type 1 (HSV-1) to cell surface chondroitin sulfate (CS) and the consequences of this interaction for virus attachment and infectivity were studied. To this end, a panel of HSV-1 gC mutants, including a gC-negative (gC(-)) variant, and mouse fibroblasts expressing either cell surface CS or heparan sulfate (HS) were used. Comparing gC-positive (gC(+)) and gC(-) viruses in terms of their attachment to and infection of CS-expressing cells indicated that gC was essential for both functions. Furthermore, purified gC bound efficiently to isolated CS chains. However, hypertonic NaCl disrupted this interaction more easily as compared to the binding of gC to HS. Also, native and selectively desulfated heparins were approximately 10 times more efficient at inhibiting gC binding to CS-expressing cells than binding to HS-expressing cells. Experiments with the HSV-1 gC mutants revealed that specific, positively charged and hydrophobic amino acids within the N-terminal part of the protein were responsible for efficient binding as well as infectivity in both CS- and HS-expressing cells. When the infectivity of the gC mutants in the two cell types was compared, it appeared that more residues contributed to the infection of CS-expressing cells than to infection of HS-expressing cells. Taken together, analysis of gC function in cell systems with limited expression of glycosaminoglycans revealed that gC could interact with either CS or HS and that these interactions exhibited subtle but definite differences as regards to the involved structural features of gC, ionic strength dependency as well as sensitivity to specifically desulfated heparin compounds.

Topics: Animals; Cell Line; Chlorocebus aethiops; Chondroitin Sulfates; Glycosaminoglycans; Heparitin Sulfate; Herpes Simplex; Herpesvirus 1, Human; Mice; Viral Envelope Proteins

Heparin added together with murine L cell interferon inhibited the development of antiviral activity in mouse L cells. When added after interferon treatment, heparin had no effect on antiviral activity. There was also no inhibition of interferon action in L cells treated with heparin before addition of interferon. On the other hand, heparin did not inhibit antiviral activities of human interferon alpha and beta. Since murine L cell interferon, but not human interferon alpha and beta, binds to a heparin affinity column and can be eluted with a solution of high salt, it is presumed that murine L cell interferon and heparin must interact with each other. The apparent interaction of heparin with murine L cell interferon was prevented by protamine, a drug that neutralizes heparin. Dextran sulfate inhibited murine L cell interferon action, but dextran and chondroitin sulfate A did not. These results suggests that heparin inhibited murine L cell interferon action by the binding via sulfate groups on its molecules. Heparin also inhibited antiviral activity of murine L cell interferon in mice infected with herpes simplex virus (+GC Miyama strain).

Topics: Animals; Chondroitin Sulfates; Chromatography, Affinity; Dextran Sulfate; Dextrans; Heparin; Heparin Antagonists; Herpes Simplex; Humans; Interferon Type I; L Cells; Mice; Mice, Inbred C3H; Protamines; Receptors, Immunologic; Receptors, Interferon; Vesicular stomatitis Indiana virus; Virus Replication