Targeting histone deacetylase activity in in vitro FMDV replication:A study with HDAC2 and HDAC8 inhibitors

Foot-and-mouth disease virus (FMDV) is a highly contagious, positive-sense RNA virus that causes severe economic losses in livestock industries worldwide. Despite widespread vaccination programs, FMDV outbreaks continue to occur, underscoring the need for deeper insights into host-virus interactions and identification of host pathways influencing viral replication. Histone deacetylases (HDACs), known epigenetic regulators, have emerged as key modulators of innate immune responses and viral pathogenesis. In this study, we investigated the role of selective HDAC2 and HDAC8 inhibition in FMDV replication using the specific inhibitors Santacruzamate A and PCI-34051, respectively, in BHK-21 cells. Viral titers and RNA levels were assessed following treatment. Although minor increases in viral titers were observed upon treatment with both inhibitors, the differences were not statistically significant (p > 0.05). Similarly, viral RNA fold change analysis showed negligible effects compared to controls. These findings suggest that HDAC2 and HDAC8 play minimal roles in regulating FMDV replication under the tested conditions. Future studies using genetic knockdown or knockout approaches are warranted to further elucidate the contribution of these HDACs to FMDV pathogenesis.