title: A novel role for 3-O-sulfated heparan sulfate in herpes simplex virus 1 entry.
abstract: Herpes simplex virus type 1 (HSV-1) binds to cells through interactions of viral glycoproteins gB and gC with heparan sulfate chains on cell surface proteoglycans. This binding is not sufficient for viral entry, which requires fusion between the viral envelope and cell membrane. Here, we show that heparan sulfate modified by a subset of the multiple D-glucosaminyl 3-O-sulfotransferase isoforms provides sites for the binding of a third viral glycoprotein, gD, and for initiation of HSV-1 entry. We conclude that susceptibility of cells to HSV-1 entry depends on (1) presence of heparan sulfate chains to which virus can bind and (2) 3-O-sulfation of specific glucosamine residues in heparan sulfate to generate gD-binding sites or the expression of other previously identified gD-binding receptors.
authors.affiliation: Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
authors.forename: D
authors.initials: D
authors.lastname: Shukla
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: P
authors.initials: P
authors.lastname: Blaiklock
authors.forename: N W
authors.initials: NW
authors.lastname: Shworak
authors.forename: X
authors.initials: X
authors.lastname: Bai
authors.forename: J D
authors.initials: JD
authors.lastname: Esko
authors.forename: G H
authors.initials: GH
authors.lastname: Cohen
authors.forename: R J
authors.initials: RJ
authors.lastname: Eisenberg
authors.forename: R D
authors.initials: RD
authors.lastname: Rosenberg
authors.forename: P G
authors.initials: PG
authors.lastname: Spear
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D016466:CHO Cells / Q000737:chemistry / Q000378:metabolism / Q000821:virology; D003001:Cloning, Molecular; D006224:Cricetinae; D004198:Disease Susceptibility; D006497:Heparan Sulfate / Q000235:genetics* / Q000378:metabolism*; D006561:Herpes Simplex / Q000503:physiopathology*; D018259:Herpesvirus 1, Human / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010957:Plasmids; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014759:Viral Envelope Proteins / Q000378:metabolism*
chemical_list: D006497:Heparan Sulfate; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus; C039447:glycoprotein D, Human herpesvirus 1; C038535:glycoprotein gC, herpes simplex virus type 1