title: Carrageenan is a potent inhibitor of papillomavirus infection.
abstract: Certain sexually transmitted human papillomavirus (HPV) types are causally associated with the development of cervical cancer. Our recent development of high-titer HPV pseudoviruses has made it possible to perform high-throughput in vitro screens to identify HPV infection inhibitors. Comparison of a variety of compounds revealed that carrageenan, a type of sulfated polysaccharide extracted from red algae, is an extremely potent infection inhibitor for a broad range of sexually transmitted HPVs. Although carrageenan can inhibit herpes simplex viruses and some strains of HIV in vitro, genital HPVs are about a thousand-fold more susceptible, with 50% inhibitory doses in the low ng/ml range. Carrageenan acts primarily by preventing the binding of HPV virions to cells. This finding is consistent with the fact that carrageenan resembles heparan sulfate, an HPV cell-attachment factor. However, carrageenan is three orders of magnitude more potent than heparin, a form of cell-free heparan sulfate that has been regarded as a highly effective model HPV inhibitor. Carrageenan can also block HPV infection through a second, postattachment heparan sulfate-independent effect. Carrageenan is in widespread commercial use as a thickener in a variety of cosmetic and food products, ranging from sexual lubricants to infant feeding formulas. Some of these products block HPV infectivity in vitro, even when diluted a million-fold. Clinical trials are needed to determine whether carrageenan-based products are effective as topical microbicides against genital HPVs.
authors.affiliation: Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, Maryland, USA.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Buck
authors.forename: Cynthia D
authors.initials: CD
authors.lastname: Thompson
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Roberts
authors.forename: Martin
authors.initials: M
authors.lastname: Müller
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Lowy
authors.forename: John T
authors.initials: JT
authors.lastname: Schiller
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000891:Anti-Infective Agents, Local / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D016466:CHO Cells; D002213:Capsid / Q000502:physiology; D002351:Carrageenan / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D002460:Cell Line; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005260:Female; D006367:HeLa Cells; D006493:Heparin / Q000737:chemistry / Q000502:physiology; D006497:Heparan Sulfate / Q000737:chemistry / Q000502:physiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D027383:Papillomaviridae / Q000187:drug effects / Q000472:pathogenicity* / Q000502:physiology; D030361:Papillomavirus Infections / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control*; D011134:Polysaccharides / Q000032:analysis / Q000737:chemistry; D015229:Sexually Transmitted Diseases, Viral / Q000188:drug therapy / Q000517:prevention & control; D014771:Virion / Q000187:drug effects / Q000472:pathogenicity / Q000502:physiology
chemical_list: D000891:Anti-Infective Agents, Local; D002351:Carrageenan; D006493:Heparin; D006497:Heparan Sulfate; D011134:Polysaccharides