Single-Cell RNA Sequencing Reveals Unique Gene Expression Profiles in porcine cells infected with attenuated Foot-and-mouth disease virus strains

Foot and mouth disease (FMD), caused by the FMD virus (FMDV), is a highly contagious disease affecting cloven-hoofed animals with significant economic implications. Modified live attenuated vaccine (LAV) candidates are being developed as countermeasures to control FMD spread, with modifications in the Leader (Lpro) region showing promise in creating attenuated strains that elicit protective immune responses. However, these strains risk reverting to virulence due to minimal genomic changes. Improving rationally designed FMDV vaccines requires a deeper understanding of virus-host interactions and how attenuation affects FMDV replication dynamics. In this study we conducted single-cell RNA (scRNA) sequencing in porcine kidney (SK6) cells infected with two attenuated strains of FMDV: one lacking the leader coding sequence (leaderless, LLV) and another with a point mutation (W105A) in Lpro, reducing its ability to cleave host ISG-conjugated proteins. These were compared to WT FMDV-infected cells. This study provided valuable insights into the cellular pathways involved in FMDV infection, ultimately helping the improvement of vaccine design.