title: Role of Filopodia in HSV-1 Entry into Zebrafish 3-O-Sulfotransferase-3-Expressing Cells.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Basic Medical Sciences, Western University of Health Sciences, Pomona, CA 91766, USA.
authors.forename: Samiksha
authors.initials: S
authors.lastname: Choudhary
authors.forename: Lorrie
authors.initials: L
authors.lastname: Burnham
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Thompson
authors.forename: Deepak
authors.initials: D
authors.lastname: Shukla
authors.forename: Vaibhav
authors.initials: V
authors.lastname: Tiwari
keywords: 3-O- sulfotransferase-3; Zebrafish; heparan sulfate; herpes simplex virus type-1; virus-cell interaction.