title: Zebrafish-encoded 3-O-sulfotransferase-3 isoform mediates herpes simplex virus type 1 entry and spread.
abstract: Heparan sulfate proteoglycans modified by human glucosaminyl 3-O-sulfotransferase-3 (3-OST-3) isoform generates the cellular receptor for herpes simplex virus type 1 (HSV-1). Interestingly, the ability of zebrafish (ZF)-encoded 3-OST-3 isoform to modify heparan sulfate to mediate HSV-1 entry and cell-cell fusion has not been determined although it is predominantly expressed in ZF, a popular model organism to study viral infections. Here, we demonstrate that expression of ZF-encoded 3-OST-3 isoform renders the resistant Chinese hamster ovary (CHO-K1) cells to become susceptible for HSV-1 entry. The following lines of evidence support the important role of ZF-encoded 3-OST-3 isoform as the mediator of HSV-1 entry into CHO-K1 cells: (1) ZF 3-OST-3-expressing CHO-K1 cells were able to preferentially bind HSV-1 glycoprotein D, and (2) CHO-K1 cells expressing ZF-encoded 3-OST-3 acquire the ability to fuse with cells expressing HSV-1 glycoproteins. Finally, knocking down 3-OST-3 receptor by siRNA in ZF fibroblasts cells significantly reduced HSV-1 entry and glycoprotein D binding to cells. Taken together, our results provide novel insight into the significance of ZF 3-OST-3 isoform as an HSV-1 entry and fusion receptor and its potential involvement in the HSV-1 disease model of ZF.
authors.affiliation: Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, California 91766, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Hubbard
authors.forename: Nissar A
authors.initials: NA
authors.lastname: Darmani
authors.forename: Gerald R
authors.initials: GR
authors.lastname: Thrush
authors.forename: Dilip
authors.initials: D
authors.lastname: Dey
authors.forename: Lorrie
authors.initials: L
authors.lastname: Burnham
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Thompson
authors.forename: Kevin
authors.initials: K
authors.lastname: Jones
authors.forename: Vaibhav
authors.initials: V
authors.lastname: Tiwari
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004797:Enzyme-Linked Immunosorbent Assay; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D006561:Herpes Simplex / Q000201:enzymology*; D018259:Herpesvirus 1, Human; D008561:Membrane Fusion / Q000502:physiology*; D008856:Microscopy, Fluorescence; D020033:Protein Isoforms / Q000378:metabolism; D034622:RNA Interference; D015238:Sulfotransferases / Q000378:metabolism*; D053586:Virus Internalization; D014779:Virus Replication / Q000502:physiology*; D015027:Zebrafish / Q000378:metabolism* / Q000821:virology*
chemical_list: D019812:Heparan Sulfate Proteoglycans; D020033:Protein Isoforms; D015238:Sulfotransferases; C021350:heparitin sulfotransferase