Filoviruses Utilize Glycosaminoglycans for Their Attachment to Target Cells |
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Authors: | Beatriz Salvador Nicole R. Sexton Ricardo Carrion Jr. Jerritt Nunneley Jean L. Patterson Imke Steffen Kai Lu Marcus O. Muench David Lembo Graham Simmons |
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Affiliation: | aBlood Systems Research Institute, San Francisco, California, USA;bDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, California, USA;cDepartment of Virology and Immunology, Texas Biomedical Research Institute, San Antonio, Texas, USA;dDepartment of Clinical and Biological Sciences, University of Turin, Turin, Italy |
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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. |
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