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

Area of Science:

• Virology
• Cell Biology
• Biochemistry

Background:

• Heparan sulfate proteoglycans (HSPGs) are modified by zebrafish (ZF) glucosaminyl 3-O sulfotransferase-3 (3-OST-3).
• This modification creates a receptor for herpes simplex virus type-1 (HSV-1) entry and spread.

Purpose of the Study:

• To elucidate the mechanism of HSV-1 entry into ZF-3-OST-3 cells.
• To investigate the role of filopodia and actin cytoskeleton rearrangement in HSV-1 infection.

Main Methods:

• High-resolution scanning electron microscopy (SEM) to observe cellular changes.
• Use of actin polymerization inhibitors (Cytochalasin-D, Lantriculin B).
• Assessment of viral infection, filopodia induction, and cell fusion.

Main Results:

• HSV-1 interaction with target cells dramatically increased filopodia formation, especially in cells expressing 3-OST-3 modified heparan sulfate (HS).
• Actin polymerization inhibitors reduced viral infection and filopodia induction, indicating actin reorganization is crucial for ZF-3-OST-3 mediated HSV-1 entry.
• Filopodia likely contribute to HSV-1 spread, as cytochalasin D pre-treatment reduced virus glycoprotein-induced cell fusion.

Conclusions:

• Filopodia are involved in HSV-1 infection of ZF-3-OST-3 cells.
• Modified heparan sulfate plays a role in cytoskeleton rearrangement during HSV-1 entry.