Zebrafish-Encoded 3-O-Sulfotransferase-3 Isoform Mediates Herpes Simplex Virus Type 1 Entry and Spread

Heparan sulfate proteoglycans modified by human glucosaminyl 3- O -sulfotransferase-3 (3- O ST-3) isoform generates the cellular receptor for herpes simplex virus type 1 (HSV-1). Interestingly, the ability of zebrafish (ZF)-encoded 3- O ST-3 isoform to modify heparan sulfate to mediate HSV-1 entry a...

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Veröffentlicht in:Zebrafish 2010-06, Vol.7 (2), p.181-187
Hauptverfasser: Hubbard, Stephen, Darmani, Nissar A., Thrush, Gerald R., Dey, Dilip, Burnham, Lorrie, Thompson, Jeffrey M., Jones, Kevin, Tiwari, Vaibhav
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Sprache:eng
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Zusammenfassung:Heparan sulfate proteoglycans modified by human glucosaminyl 3- O -sulfotransferase-3 (3- O ST-3) isoform generates the cellular receptor for herpes simplex virus type 1 (HSV-1). Interestingly, the ability of zebrafish (ZF)-encoded 3- O ST-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- O ST-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- O ST-3 isoform as the mediator of HSV-1 entry into CHO-K1 cells: (1) ZF 3- O ST-3–expressing CHO-K1 cells were able to preferentially bind HSV-1 glycoprotein D, and (2) CHO-K1 cells expressing ZF-encoded 3- O ST-3 acquire the ability to fuse with cells expressing HSV-1 glycoproteins. Finally, knocking down 3- O ST-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- O ST-3 isoform as an HSV-1 entry and fusion receptor and its potential involvement in the HSV-1 disease model of ZF.
ISSN:1545-8547
1557-8542
DOI:10.1089/zeb.2009.0621