Role of Filopodia in HSV-1 Entry into Zebrafish 3-O-Sulfotransferase-3-Expressing Cells

Samiksha Choudhary 1, Lorrie Burnham 2, Jeffrey M Thompson 3, Deepak Shukla 4, Vaibhav Tiwari*, 5
1 Department of Basic Medical Sciences, Western University of Health Sciences, Pomona, CA 91766, USA
2 San Bernardino Valley College, San Bernardino, CA 92410, USA
3 California State University, San Bernardino, CA 92407, USA
4 Departments of Ophthalmology and Visual Sciences & Microbiology/Immunology, University of Illinois at Chicago IL 60612, USA
5 Department of Microbiology & Immunology, Midwestern University, Downers Grove, IL 60515, USA

© Choudhary et al.; Licensee Bentham Open.

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* Address correspondence to this author at the Department of Microbiology & Immunology, Midwestern University, Downers Grove IL 60515, USA; Fax: + 1 630-515-6358; E-mail:



Heparan sulfate proteoglycans (HSPGs) modified by zebrafish (ZF) encoded glucosaminyl 3-O sulfotransferase-3 (3-OST-3) generate a receptor for herpes simplex virus type-1 (HSV-1) entry and spread. In order to elucidate the mechanism by which HSV-1 enters into ZF-3-OST-3 cells, we investigated the mode of viral entry.


Under high resolution scanning electron microscopy (SEM), actin cytoskeleton changes were observed by a dramatic increase in the number of filopodia formed during early interactions of HSV-1 with the target cells. While the increase in number was common among all the infected cells, the highest numbers of filopodia was observed in cells expressing the 3-OST-3 modified form of heparan sulfate (HS) encoded either by human or ZF. The levels of viral infection and filopodia induction were reduced with the actin polymerization inhibitors, Cytochalasin-D and Lantriculin B, suggesting an important role for actin reorganization during ZF-3-OST-3 mediated HSV-1 entry. Supporting an interesting possibility of filopodia usage during HSV-1 spread, pre-treatment of cytochalasin D in ZF-3-OST-3 cells drastically reduced virus glycoprotein induced cell fusion.


Taken together, our results provide new evidence on the involvement of filopodia during HSV-1 infection of ZF-3-OST-3 cells and confirm a role for modified heparan sulfate in cytoskeleton rearrangement during HSV-1 entry.

Keywords: Zebrafish, heparan sulfate, herpes simplex virus type-1, 3-O- sulfotransferase-3, virus-cell interaction..