Deciphering foot-and-mouth disease (FMD) virus-host tropism

Area of Science:

• Veterinary Virology
• Molecular Interactions
• Structural Biology

Background:

• Foot and Mouth Disease virus (FMDV) tropism is mediated by interactions between its viral protein 1 (VP1) and host cell integrins.
• Understanding these molecular interactions is crucial for developing effective FMDV control strategies.

Purpose of the Study:

• To decipher the interaction patterns between FMDV VP1 and host integrins in susceptible and resistant species.
• To investigate the impact of site-directed mutations on these interactions using structural modeling and validation.

Main Methods:

• Utilized predicted and validated 3D structures of FMDV VP1, mutated VP1, and integrins from *Bos taurus*, *Gallus*, and *Canis*.
• Performed *in-silico* site-directed mutagenesis to assess the role of specific protein motifs.
• Conducted *in-vitro* analysis to confirm the persistence of tropism sites in cattle breeds.

Main Results:

• Identified strong interactions between FMDV VP1 motifs (RGD and SIPLQ) and *Bos taurus* alpha-integrin.
• Demonstrated that *in-silico* mutation of the RGD domain in FMDV VP1 completely abolished interaction with *B. taurus* integrin.
• Confirmed the presence of the 'SIPLQ' tropism site in various cattle breeds through *in-vitro* assays.

Conclusions:

• The arginine-glycine-aspartic acid (RGD) domain of FMDV VP1 plays a critical role in host integrin binding.
• The 'SIPLQ' motif is conserved and potentially contributes to FMDV tropism in cattle.
• Deciphering these host-receptor interactions can inform the development of new FMDV vaccines and therapeutic strategies.