Heparan sulfate is an attachment factor for foamy virus entry

Area of Science:

• Virology
• Cell Biology
• Glycobiology

Background:

• The cellular receptor for foamy viruses (FVs) remains unidentified.
• The wide range of permissive cells suggests a ubiquitous cellular structure is involved.
• Heparan sulfate (HS), a glycosaminoglycan (GAG), is abundant on the extracellular matrix of many cell types.

Purpose of the Study:

• To investigate if heparan sulfate (HS) acts as a cellular receptor for foamy viruses (FVs).
• To determine the role of HS in binding and entry of prototype FV (PFV) and feline FV (FFV).

Main Methods:

• Correlated FV permissivity with cell surface HS expression across various cell lines.
• Assessed PFV entry inhibition after enzymatic digestion of cell surface HS.
• Utilized fast protein liquid chromatography (FPLC) with heparin to detect FV particle binding.
• Tested the effect of soluble heparin on PFV and FFV infection.

Main Results:

• FV cell entry permissivity strongly correlated with cell surface HS levels (P < 0.001).
• Enzymatic removal of HS reduced PFV entry by at least 500-fold.
• FV particles bound to heparin in FPLC, and soluble heparin inhibited PFV and FFV infection.

Conclusions:

• Foamy viruses (FVs) bind to heparan sulfate (HS) on the cell surface.
• HS is a critical attachment factor facilitating FV entry into host cells.
• This interaction is a pivotal step in the foamy virus life cycle.