<b>A class IIa HDACs inhibitor TMP269 restricts Peste des petits ruminants virus replication and reduces inflammation induced by virus infection</b>

Peste des petits ruminants (PPR) is an acute and fatal contagious disease, caused by the PPR virus (PPRV), and is one of the most damaging animal diseases. The replication of many viruses is closely related to the regulation of histone deacetylases (HDACs). TMP269, a selective class IIa HDAC inhibitor, plays an important role in cancer therapy and can modulate viral replication. However, the regulatory effects of TMP269 on PPRV replication remain poorly understood. Here, we found that TMP269 exerted a strong inhibitory effect on PPRV replication. RNA sequencing (RNA-seq) analysis showed that the upregulated expression of genes associated with inflammatory responses upon PPRV infection was significantly downregulated by TMP269 treatment. Further Quantitative Real-time PCR (qRT-PCR) analysis and ELISA experiments demonstrated that TMP269 decreased the expression of the pro-inflammatory chemokines CCL2, CCL5, CCL7, CXCL8, and cytokine IL-6 during infection, suggesting the vital role of TMP269 in anti-inflammatory processes. Collectively, our findings suggest that the HDAC inhibitor TMP269 is a promising antiviral agent for PPRV and provide novel insights into the antiviral and anti-inflammatory abilities of TMP269.