A role for heparan sulfate 3-O-sulfotransferase isoform 2 in herpes simplex virus type 1 entry and spread.
Heparan sulfate (HS) 3-O-sulfotransferase isoform-2 (3-OST-2), which belongs to a family of enzymes capable of generating herpes simplex virus type-1 (HSV-1) entry and spread receptors, is predominantly expressed in human brain. Despite its unique expression pattern, the ability of 3-OST-2 to mediate HSV-1 entry and cell-to-cell fusion is not known. Our results demonstrate that expression of 3-OST-2 can render Chinese hamster ovary K1 (CHO-K1) cells susceptible to entry of wild-type and mutant strains of HSV-1. Evidence for generation of gD receptors by 3-OST-2 were suggested by gD-mediated interference assay and the ability of 3-OST-2-expressing CHO-K1 cells to preferentially bind HSV-1 gD, which could be reversed by prior treatment of cells with HS lyases (heparinases II/III). In addition, 3-OST-2-expressing CHO-K1 cells acquired the ability to fuse with cells-expressing HSV-1 glycoproteins, a phenomenon that mimics a way of viral spread in vivo. Demonstrating specificity, the cell fusion was inhibited by soluble 3-O-sulfated forms of HS, but not unmodified HS. Taken together, our results raise the possibility of a role of 3-OST-2 in the spread of HSV-1 infection in the brain.
O'Donnell
Christopher D
CD
Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.
Tiwari
Vaibhav
V
Oh
Myung-Jin
MJ
Shukla
Deepak
D
D000818:Animals; D016466:CHO Cells; D002459:Cell Fusion; D006224:Cricetinae; D017930:Genes, Reporter; D006497:Heparan Sulfate / Q000378:metabolism; D018259:Herpesvirus 1, Human / Q000502:physiology*; D006801:Humans; D007527:Isoenzymes / Q000502:physiology*; D008156:Luciferases / Q000032:analysis; D011991:Receptors, Virus / Q000502:physiology*; D015238:Sulfotransferases / Q000502:physiology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism
D006497:Heparan Sulfate; D007527:Isoenzymes; D008156:Luciferases; D011991:Receptors, Virus; D015238:Sulfotransferases; D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1; C021350:heparitin sulfotransferase