Sulfated polymers inhibit the interaction of human cytomegalovirus with cell surface heparan sulfate.
Several sulfated polysaccharides (dextran sulfate, pentosan polysulfate, heparin) and copolymers of acrylic acid with vinylalcohol sulfate have proved to be potent inhibitors of human cytomegalovirus (CMV) infectivity in vitro. Sulfated alpha-cyclodextrins are only weak inhibitors of CMV. A close correlation was found between the 50% inhibitory concentrations of the sulfated polymers for CMV cytopathogenicity, virus-cell binding, and expression of immediate early antigens (IEA) in human embryonic lung (HEL) cells. CMV particles bound specifically to heparin-Sepharose. Sulfated polymers specifically eluted the virus particles from this matrix. Enzymatic digestion of cell surface heparan sulfate, but not of chondroitin sulfate, prevented the cells from being infected with CMV. Moreover, radiolabeled CMV bound efficiently to, and were infective for wild-type Chinese hamster ovary (CHO) cells, whereas virus binding to, and infection of, mutant CHO cell lines that were deficient in either all glycosaminoglycans or heparan sulfate only was significantly impaired. The mechanism of action of the sulfated polymers can be attributed to an inhibitory effect on the binding of CMV particles to the host cells. Presumably, the sulfated polymers interact with the viral envelope site(s) involved in the attachment of the CMV virions to cell surface heparan sulfate.
Neyts
J
J
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
Snoeck
R
R
Schols
D
D
Balzarini
J
J
Esko
J D
JD
Van Schepdael
A
A
De Clercq
E
E
D000180:Acrylic Resins / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D002810:Chondroitinases and Chondroitin Lyases / Q000378:metabolism; D006224:Cricetinae; D003505:Cyclodextrins / Q000494:pharmacology; D003587:Cytomegalovirus / Q000187:drug effects / Q000378:metabolism* / Q000472:pathogenicity; D016264:Dextran Sulfate / Q000494:pharmacology; D006025:Glycosaminoglycans / Q000235:genetics; D006493:Heparin / Q000494:pharmacology; D019763:Heparin Lyase; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans; D010426:Pentosan Sulfuric Polyester / Q000494:pharmacology; D011108:Polymers / Q000494:pharmacology*; D011133:Polysaccharide-Lyases / Q000378:metabolism; D013464:Sulfuric Acids / Q000494:pharmacology; D014158:Transcription, Genetic; D014779:Virus Replication / Q000187:drug effects*
D000180:Acrylic Resins; D002810:Chondroitinases and Chondroitin Lyases; D003505:Cyclodextrins; D016264:Dextran Sulfate; D006025:Glycosaminoglycans; D006493:Heparin; D019763:Heparin Lyase; D006497:Heparan Sulfate; D010426:Pentosan Sulfuric Polyester; D011108:Polymers; D011133:Polysaccharide-Lyases; D013464:Sulfuric Acids; C063252:sulfated acrylic acid-vinyl alcohol copolymer; C063253:sulfated polyvinyl alcohol; C021349:heparitinsulfate lyase