The ubiquitin proteasome system is necessary for efficient proliferation of porcine reproductive and respiratory syndrome virus

•Proteasome inhibitor MG132 inhibits PRRSV proliferation in a dose-dependent manner.•MG132 inhibits PRRSV proliferation at the adsorption and replication steps.•PRRSV infection alters the expression profile of cellular ubiquitin.•Overexpression of ubiquitin partially reverses the MG132 inhibitory effect on PRRSV. The ubiquitin-proteasome system (UPS) plays a vital role in cellular protein homeostasis by ensuring protein quality control and maintaining a critical level of important regulatory proteins. Thus, it is not surprising that the functional UPS is manipulated by viruses to assist in viral propagation. Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically significant swine disease that has been devastating the swine industry worldwide. However, the role of UPS in PRRSV infection is unknown. In this study, we found that treatment with the proteasome inhibitor MG132 significantly inhibited PRRSV proliferation in a dose-dependent manner. The anti-PRRSV effect of MG132 was most significant in the middle stage of the PRRSV lifecycle, which is achieved via inhibition of viral attachment and replication. Interestingly, the expression of poly-ubiquitin was drastically decreased and the accumulation of free-ubiquitin was obviously elevated in the middle stage of PRRSV infection. Furthermore, the ectopic expression of ubiquitin in MG132-treated cells partially reversed the inhibitory effect of MG132 on PRRSV proliferation. Taken together, these results suggest that PRRSV manipulates UPS to promote self-proliferation by cheating or taking advantage of the host proteasome, degrading intracellular poly-ubiquitin and increasing the accumulation of free ubiquitin.