title: Filoviruses utilize glycosaminoglycans for their attachment to target cells.
abstract: Filoviruses are the cause of severe hemorrhagic fever in human and nonhuman primates. The envelope glycoprotein (GP), responsible for both receptor binding and fusion of the virus envelope with the host cell membrane, has been demonstrated to interact with multiple molecules in order to enhance entry into host cells. Here we have demonstrated that filoviruses utilize glycosaminoglycans, and more specifically heparan sulfate proteoglycans, for their attachment to host cells. This interaction is mediated by GP and does not require the presence of the mucin domain. Both the degree of sulfation and the structure of the carbohydrate backbone play a role in the interaction with filovirus GPs. This new step of filovirus interaction with host cells can potentially be a new target for antiviral strategies. As such, we were able to inhibit filovirus GP-mediated infection using carrageenan, a broad-spectrum microbicide that mimics heparin, and also using the antiviral dendrimeric peptide SB105-A10, which interacts with heparan sulfate, antagonizing the binding of the virus to cells.
authors.affiliation: Blood Systems Research Institute, San Francisco, CA, USA. bsalvador@bloodsystems.org
authors.forename: Beatriz
authors.initials: B
authors.lastname: Salvador
authors.forename: Nicole R
authors.initials: NR
authors.lastname: Sexton
authors.forename: Ricardo
authors.initials: R
authors.lastname: Carrion
authors.forename: Jerritt
authors.initials: J
authors.lastname: Nunneley
authors.forename: Jean L
authors.initials: JL
authors.lastname: Patterson
authors.forename: Imke
authors.initials: I
authors.lastname: Steffen
authors.forename: Kai
authors.initials: K
authors.lastname: Lu
authors.forename: Marcus O
authors.initials: MO
authors.lastname: Muench
authors.forename: David
authors.initials: D
authors.lastname: Lembo
authors.forename: Graham
authors.initials: G
authors.lastname: Simmons
mesh_terms: D000818:Animals; D002460:Cell Line; D016563:Filoviridae / Q000502:physiology*; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D006801:Humans; D011991:Receptors, Virus / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000378:metabolism*; D053585:Virus Attachment
chemical_list: D019812:Heparan Sulfate Proteoglycans; D011991:Receptors, Virus; D014759:Viral Envelope Proteins