Zebrafish 3-O-Sulfotransferase-4 Generated Heparan Sulfate Mediates HSV-1 Entry and Spread
- Authors
- Antoine, T.E., Yakoub, A., Maus, E., Shukla, D., and Tiwari, V.
- ID
- ZDB-PUB-140415-2
- Date
- 2014
- Source
- PLoS One 9(2): e87302 (Journal)
- Registered Authors
- Tiwari, Vaibhav
- Keywords
- none
- MeSH Terms
-
- Animals
- CHO Cells
- Cell Fusion
- Cricetinae
- Cricetulus
- Gene Expression Regulation, Enzymologic
- Heparitin Sulfate/metabolism*
- Herpesvirus 1, Human/genetics
- Herpesvirus 1, Human/metabolism*
- Herpesvirus 1, Human/physiology
- Humans
- Isoenzymes/genetics
- Isoenzymes/metabolism
- Microscopy, Confocal
- Polysaccharide-Lyases/metabolism
- Reverse Transcriptase Polymerase Chain Reaction
- Sulfotransferases/genetics
- Sulfotransferases/metabolism*
- Viral Envelope Proteins/genetics
- Viral Envelope Proteins/metabolism
- Virus Internalization*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 24498308 Full text @ PLoS One
Rare modification of heparan sulfate (HS) by glucosaminyl 3-O sulfotransferase (3-OST) isforms 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.