Zebrafish 3-O-sulfotransferase-4 generated heparan sulfate mediates HSV-1 entry and spread.
Rare modification of heparan sulfate (HS) by glucosaminyl 3-O sulfotransferase (3-OST) isoforms generates an entry receptor for herpes simplex virus type-1 (HSV-1). In the zebrafish (ZF) model multiple 3-OST isoforms are differentially expressed. One such isoform is 3-OST-4 which is widely expressed in the central nervous system of ZF. In this report we characterize the role of ZF encoded 3-OST-4 isoform for HSV-1 entry. Expression of ZF 3-OST-4 into resistant Chinese hamster ovary (CHO-K1) cells promoted susceptibility to HSV-1 infection. This entry was 3-O sulfated HS (3-OS HS) dependent as pre-treatment of ZF 3-OST-4 cells with enzyme HS lyases (heparinase II/III) significantly reduced HSV-1 entry. Interestingly, co-expression of ZF 3-OST-4 along with ZF 3-OST-2 which is also expressed in brain rendered cells more susceptible to HSV-1 than 3-OST-4 alone. The role of ZF-3-OST-4 in the spread of HSV-1 was also evaluated as CHO-K1 cells that expressed HSV-1 glycoproteins fused with ZF 3-OST-4 expressing effector CHO-K1 cells. Finally, adding further evidence ZF 3-OST-4 mediated HSV-1 entry was inhibited by anti-3O HS G2 peptide. Taken together our results demonstrate a role for ZF 3-OST-4 in HSV-1 pathogenesis and support the use of ZF as a model to study it.
Departments of Ophthalmology and Visual Sciences & Microbiology/Immunology, University of Illinois at Chicago, Chicago, Illinois, United States of America.
Thessicar E
TE
Antoine
Departments of Ophthalmology and Visual Sciences & Microbiology/Immunology, University of Illinois at Chicago, Chicago, Illinois, United States of America.
Abraam
A
Yakoub
Department of Microbiology and Immunology, Midwestern University, Downers Grove, Illinois, United States of America.
Erika
E
Maus
Departments of Ophthalmology and Visual Sciences & Microbiology/Immunology, University of Illinois at Chicago, Chicago, Illinois, United States of America.
Deepak
D
Shukla
Departments of Ophthalmology and Visual Sciences & Microbiology/Immunology, University of Illinois at Chicago, Chicago, Illinois, United States of America ; Department of Microbiology and Immunology, Midwestern University, Downers Grove, Illinois, United States of America.
Vaibhav
V
Tiwari
D000818:Animals; D016466:CHO Cells; D002459:Cell Fusion; D006224:Cricetinae; D003412:Cricetulus; D015971:Gene Expression Regulation, Enzymologic; D006497:Heparan Sulfate / Q000378:metabolism*; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D011133:Polysaccharide-Lyases / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism; D053586:Virus Internalization; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D006497:Heparan Sulfate; D007527:Isoenzymes; D011133:Polysaccharide-Lyases; D015238:Sulfotransferases; D014759:Viral Envelope Proteins; D029961:Zebrafish Proteins; C093554:heparin-glucosamine 3-O-sulfotransferase; C114663:heparinase II; C021349:heparitinsulfate lyase