MG132 Attenuates the Replication of Classical Swine Fever Virus in vitro

Abstract

The 26S proteasome, in charge of intracellular protein degradation, plays significant roles in the modulation of various cellular activities as well as in the interplay between virus and host. However, studies about the relationship between 26S proteasome and classical swine fever virus (CSFV) is limited up to now. MG132 is a proteasome inhibitor and has been extensively used in studies about replication of many viruses. Herein, we investigated the role of MG132 in CSFV replication and results showed that MG132 significantly decreased virus titers and viral RNA copies in CSFV-infected PK-15 cells. Further studies demonstrated that MG132 upregulated the expression of several interferon-stimulated genes (ISGs), in CSFV-infected cells. Since the activation of ISGs is controlled by the JAK-STAT signal pathway, we next examined the effect of MG132 on the expression and localization of key molecular STAT1 in the infected cells using Western blot and confocal laser scanning microscopy, respectively. Results showed that CSFV infection and viral NS4A protein decreased the protein level of STAT1, and MG132 promoted the accumulation of STAT1 in the nucleus of cells adjacent to the CSFVinfected cells. Besides, MG132 did not affect the expressions of IFN-α, STAT1, Mx1, OAS1, and PKR genes in cells without CSFV. In conclusion, we identify that MG132 significantly inhibits CSFV replication in vitro, in which the activation of the JAK-STAT pathway and the subsequent upregulation of expressions of ISGs might play significant roles, providing a potential preventive method for CSF.

The Network of Interactions Between Classical Swine Fever Virus Nonstructural Protein p7 and Host Proteins

“…This speculation was consistent with our previous work, which demonstrated that the increase of [Ca 2+ ] cyto mediated by CSFV infection could potently induce autophagy via the CAMKK2 (calcium/calmodulin-dependent protein kinase kinase 2) -PRKAA (protein kinase AMP-activated catalytic subunit alpha) -MTOR (mechanistic target of rapamycin kinase) pathway (Xie et al, 2020). Our previous study also showed that the JAK-STAT pathway might play a significant role in CSFV infection (Chen et al, 2020). In the present study, PIAS1, a protein inhibitor of activated STAT 1, was found to be a potential binding partner of the CSFV p7, implying that p7 might regulate the JAK-STAT pathway by interacting with PIAS1 (Figure 6).…”

“…1 JAK-STAT pathway. Our previous study revealed that the JAK-STAT pathway might play a significant role in CSFV infection (Chen et al, 2020). In the present study, PIAS1 (protein inhibitor of activated STAT 1) was found to be a potential binding partner of the CSFV p7, which suggested that p7 might regulate the JAK-STAT pathway by interacting with PIAS1.…”

The function role of ubiquitin proteasome pathway in the ER stress-induced AECII apoptosis during hyperoxia exposure

“…UPP is another major protein degradation system in eukaryotes besides lysosomal pathway. The target protein is ubiquitinated through a series of enzymatic reactions and specifically recognized and degraded by 26 s proteasome [ 17 , 38 ]. The dysfunction of UPP is related to the pathogenesis of some human diseases.…”

Anti-Classical Swine Fever Virus Strategies

“…(8) The proteasome is involved in the interplay between many viruses and hosts. MG132 [119], a proteasome inhibitor, could attenuate the CSFV replication. (9) Other molecules also have anti-CSFV effects, such as Prostaglandin A1 [120,121], the phage-displayed E2-binding peptides [122], ceramide (C6) (activator of the protein phosphatase 1 pathway) [123], and quercetin (inhibitor of HSP70 function) [88].…”