title: Zebrafish encoded 3-O-sulfotransferase-2 generated heparan sulfate serves as a receptor during HSV-1 entry and spread.
abstract: Previously we reported the role of zebrafish (ZF) encoded glucosaminyl 3-O-sulfotransferase-3 (3-OST-3) isoform in assisting herpes simplex virus type-1 (HSV-1) entry and spread by generating an entry receptor to HSV-1 envelope glycoprotein D (gD). However, the ability of ZF encoded 3-OST-2 isoform to participate in HSV-1 entry has not been determined although it is predominantly expressed in ZF brain, a prime target for HSV-1 to infect and establish lifelong latency. Here we report the expression cloning of ZF encoded 3-OST-2 isoform and demonstrate HSV-1 entry into resistant Chinese hamster ovary (CHO-K1) cells expressing the clone. Additional significance of ZF encoded 3-OST-2 receptor was demonstrated using medically important isolates of HSV-1. In addition, interference to HSV-1 entry was observed upon co-expression of HSV-1 gD and ZF 3-OST-2. Similarly HSV-1 entry was significantly inhibited by the pre-treatment of cells with enzyme HS lyases (heparinase II/III). Finally, ZF-3-OST-2 expressing CHO-K1 was able to fuse with HSV-1 glycoprotein expressing cells suggesting their role in HSV-1 spread. Taken together our result demonstrates a role for ZF 3-OST-2 in HSV-1 pathogenesis.
authors: Department of Microbiology & Immunology, Midwestern University, Downers Grove, IL 60515, USA.
authors: John
authors: J
authors: Baldwin
authors: Thessicar E
authors: TE
authors: Antoine
authors: Deepak
authors: D
authors: Shukla
authors: Vaibhav
authors: V
authors: Tiwari
mesh_terms: D000818:Animals; D016466:CHO Cells; D002459:Cell Fusion; D006224:Cricetinae; D006497:Heparan Sulfate / Q000502:physiology*; D018259:Herpesvirus 1, Human / Q000502:physiology*; D011991:Receptors, Virus / Q000378:metabolism*; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism; D053586:Virus Internalization; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D006497:Heparan Sulfate; D011991:Receptors, Virus; D015238:Sulfotransferases; D014759:Viral Envelope Proteins; D029961:Zebrafish Proteins; C040495:glycoprotein B, Simplexvirus; C518416:heparan sulfate 2-O-sulfotransferase, zebrafish; C583640:heparan sulfate 3-O-sulfotransferase, zebrafish