USP8 suppresses porcine reproductive and respiratory syndrome virus replication by positively regulating MAVS mediated Ⅰ-IFN signaling

Porcine reproductive and respiratory syndrome virus (PRRSV) is an important RNA virus that has caused huge economic losses to swine industry in the whole world. Ubiquitin specific protease 8 (USP8), a pivotal regulator of protein degradation, intricately contributes to orchestrating the delicate balance of various biological processes through its deubiquitinating activity. However, the role of USP8 in antiviral immune response to PRRSV remains elusive. In the study, by means of overexpressing USP8, we identified that USP8 suppressed the replication of PRRSV, while reducing USP8 expression using siRNA significantly led to the promotion of PRRSV replication. And USP8 facilitates the production of IFN-β and some IFN-stimulated genes (ISGs) during PRRSV infection. Mechanistically, USP8 promoted mitochondrial antiviral signaling protein (MAVS)-mediated IFN-β signaling. Moreover, USP8 interacted with MAVS and exerted anti-PRRSV effects in a MAVS-dependent manner. This study highlights the importance of USP8 in regulating PRRSV replication, which may enhance our comprehension of its role in innate immunity and its impact on viral replication.