Recognition of heparan sulfate by clinical strains of dengue virus serotype 1 using recombinant subviral particles
Autor: | Boris K. Gavrilov, Ram Sasisekharan, Luke Robinson, Troy T. Rurak, Mathuros Ruchirawat, Charlermchai Artpradit |
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Přispěvatelé: | Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. School of Engineering, Koch Institute for Integrative Cancer Research at MIT, Robinson, Luke N., Gavrilov, Boris K., Rurak, Troy T., Sasisekharan, Ram |
Jazyk: | angličtina |
Rok vydání: | 2013 |
Předmět: |
Serotype
Cancer Research 030231 tropical medicine Virus Attachment Heparan sulfate Dengue virus Biology medicine.disease_cause Antiviral Agents Article Dengue fever law.invention Microbiology Cell Line Dengue 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine law Virology medicine Animals Humans Receptor 030304 developmental biology 0303 health sciences Heparin Chondroitin Sulfates Recombinant subviral particle Dengue Virus medicine.disease 3. Good health Infectious Diseases chemistry Cell culture Recombinant DNA Receptors Virus Heparitin Sulfate medicine.drug |
Zdroj: | Virus research Elsevier |
ISSN: | 1872-7492 0168-1702 |
Popis: | Dengue is the most important arthropod-borne viral disease in humans, with an estimated 3.6 billion people at risk for infection and more than 200 million infections per year. Identification of the cellular receptors for dengue virus (DV), the causative agent of dengue, is important toward understanding the pathogenesis of the disease. Heparan sulfate (HS) has been characterized as a DV receptor in multiple model systems, however the physiological relevance of these findings has been questioned by observations that flaviviruses, including DV, can undergo cell culture adaptation changes resulting in increased binding to HS. It thus remains unclear whether HS is utilized by clinical, non-cell culture-adapted strains of DV. To address this question, herein we describe a set of methodologies using recombinant subviral particles (RSPs) to determine the utilization of HS by clinical strains of DV serotype 1 (DV1). RSPs of clinically isolated strains with low cell culture passage histories were used to study HS interaction. Biochemically characterized RSPs showed dose-dependent binding to immobilized heparin, which could be competed by heparin and HS but not structurally related glycosaminoglycans chondroitin sulfate A and hyaluronic acid. The relevance of heparin and HS biochemical interactions was demonstrated by competition of RSP and DV binding to cells with soluble heparin and HS. Our results demonstrate that clinical strains of DV1 can specifically interact with heparin and HS. Together, these data support the possibility that HS on cell surfaces is utilized in the DV-human infection process. National Institutes of Health (U.S.) (R37 GM057073-13) Singapore-MIT Alliance for Research and Technology |
Databáze: | OpenAIRE |
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