Dengue Virus Infectivity Depends on Envelope Protein Binding to Target Cell Heparan Sulfate

Chen, Yaping
Maguire, Terry
Hileman, Ronald E.
Fromm, Jonathan R.
Esko, Jeffrey D.
Linhardt, Robert J.
Marks, Rory M.
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Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Dengue Virus Infectivity Depends on Envelope Protein Binding toTarget Cell Heparan Sulfate, Y. Chen, T. Maguire, R. E. Hileman, J. R.Fromm, J. D. Esko, R.J. Linhardt, R. M. Marks, Nature Medicine,3,866-871, 1997.
Dengue virus is a human pathogen that has reemerged as an increasingly important public health threat. We found that the cellular receptor utilized by dengue envelope protein to bind to target cells is a highly sulfated type of heparan sulfate. Heparin, highly sulfated heparan sulfate, and the polysulfonate pharmaceutical Suramin effectively prevented dengue virus infection of target cells, indicating that the envelope protein-target cell receptor interaction is a critical determinant of infectivity. The dengue envelope protein sequence includes two putative glycosaminoglycan-binding motifs at the carboxy terminus; the first could be structurally modeled and formed an unusual extended binding surface of basic amino acids. Similar motifs were also identified in the envelope proteins of other flaviviridae. Developing pharmaceuticals that inhibit target cell binding may be an effective strategy for treating flavivirus infections.
Nature Medicine, 3, 866-871
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The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
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Rensselaer Polytechnic Institute, Troy, NY
Nature Medicine