Isolation and characterisation of potential respiratory syncytial virus receptor(s) on epithelial cells

Area of Science:

• Virology
• Cell Biology
• Drug Discovery

Background:

• Respiratory syncytial virus (RSV) causes severe lower respiratory tract infections, particularly in infants and the elderly.
• Current therapies for RSV infections are largely ineffective, necessitating the search for novel drug targets.
• Understanding RSV adhesion mechanisms is crucial for developing new antiviral strategies.

Purpose of the Study:

• To identify and characterize the RSV adhesion receptor on mammalian cells.
• To explore potential therapeutic targets for RSV infection based on receptor interactions.
• To investigate the role of annexin II in RSV binding and infection.

Main Methods:

• Utilized soluble human lectins, complex polysaccharides, and a selectin antagonist (TBC1269) to characterize the RSV receptor on Hep2 cells.
• Assessed the inhibitory effects of carbohydrate-based selectin antagonists (fucoidan, TBC1269) on RSV infection in vitro and in a mouse model.
• Isolated and characterized annexin II as a potential RSV receptor, examining its binding interactions with RSV G-protein, heparin, and plasminogen.

Main Results:

• The RSV receptor on Hep2 cells exhibited binding characteristics similar to L-selectin.
• Selectin antagonists fucoidan and TBC1269 demonstrated inhibition of RSV infection both in vitro and in vivo.
• Annexin II was identified as a potential RSV receptor, with its expression increasing post-infection.
• Recombinant annexin II bound to RSV G-protein, heparin, and plasminogen, with binding inhibited by TBC1269.

Conclusions:

• Annexin II is a potential RSV receptor involved in viral adhesion.
• Inhibitors targeting annexin II show promise for the development of novel therapies against RSV infection.
• Selectin antagonists represent a viable strategy for combating RSV infections.