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Zebrafish. 2010 Jun;7(2):181-7. doi: 10.1089/zeb.2009.0621.

Zebrafish-encoded 3-O-sulfotransferase-3 isoform mediates herpes simplex virus type 1 entry and spread.

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  • 1Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, California 91766, USA.


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.

[PubMed - indexed for MEDLINE]
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