Dengue virus infectivity depends on envelope protein binding to target cell heparan sulfate.
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.
Chen
Y
Y
Department of Internal Medicine, University of Michigan, Ann Arbor 48109, USA.
Maguire
T
T
Hileman
R E
RE
Fromm
J R
JR
Esko
J D
JD
Linhardt
R J
RJ
Marks
R M
RM
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003716:Dengue Virus / Q000378:metabolism / Q000472:pathogenicity*; D006025:Glycosaminoglycans / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology; D006497:Heparan Sulfate / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D011485:Protein Binding; D011991:Receptors, Virus / Q000378:metabolism; D013498:Suramin / Q000494:pharmacology; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000378:metabolism*; D014774:Virulence / Q000187:drug effects
D006025:Glycosaminoglycans; D006493:Heparin; D006497:Heparan Sulfate; D011991:Receptors, Virus; D013498:Suramin; D014759:Viral Envelope Proteins