title: A role for 3-O-sulfotransferase isoform-4 in assisting HSV-1 entry and spread.
abstract: Many heparan sulfate (HS) 3-O-sulfotransferase (3-OST) isoforms generate cellular receptors for herpes simplex virus type-1 (HSV-1) glycoprotein D (gD). Interestingly, the ability of 3-OST-4 to mediate HSV-1 entry and cell-to-cell fusion has not been determined, although it is predominantly expressed in the brain, a primary target of HSV-1 infections. We report that expression of 3-OST-4 can render Chinese hamster ovary K1 (CHO-K1) cells susceptible to entry of wild-type and a mutant (Rid1) strain of HSV-1. Evidence for generation of gD receptors by 3-OST-4 was suggested by gD-mediated interference assay and the ability of 3-OST-4 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-4 expressing CHO-K1 cells acquired the ability to fuse with cells-expressing HSV-1 glycoproteins. Demonstrating specificity, the cell fusion was inhibited by soluble 3-O-sulfated forms of HS, but not unmodified HS. Taken together our results suggest a role of 3-OST-4 in HSV-1 pathogenesis.
authors.affiliation: Department of Ophthalmology and Visual Sciences, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Vaibhav
authors.initials: V
authors.lastname: Tiwari
authors.forename: Christopher D
authors.initials: CD
authors.lastname: O'Donnell
authors.forename: Myung-Jin
authors.initials: MJ
authors.lastname: Oh
authors.forename: Tibor
authors.initials: T
authors.lastname: Valyi-Nagy
authors.forename: Deepak
authors.initials: D
authors.lastname: Shukla
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D018259:Herpesvirus 1, Human / Q000502:physiology*; D008561:Membrane Fusion / Q000502:physiology*; D020033:Protein Isoforms / Q000378:metabolism; D015238:Sulfotransferases / Q000378:metabolism*; D014779:Virus Replication / Q000502:physiology*
chemical_list: D020033:Protein Isoforms; D015238:Sulfotransferases; C021350:heparitin sulfotransferase