The IFN-γ-induced immunoproteasome is suppressed in highly pathogenic porcine reproductive and respiratory syndrome virus-infected alveolar macrophages

Abstract

Highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) evades cytotoxic T lymphocyte (CTL) responses through interactions between viral Nsp1α and Nsp4 and β2 M heavy and light chains, respectively, of swine leukocyte antigen class (SLA)-I. However, whether the immunoproteasome (i-proteasome) complex, which is an important component of the antigen delivery pathway that functions by mediating peptide production, is also affected by viral infection is unknown. In this study, we investigated the effects of HP-PRRSV (HuN4-F5) infection on IFN-γ-induced i-proteasome expression using a cell culture system (alveolar macrophages, AMs). We found that this virus inhibited the expression of IFN-γ-induced i-proteasome subunits LMP2, LMP7, and MECL-1 at the mRNA and protein level. In addition, expression levels of the i-proteasome regulatory subunits PSME1 and PSME2 in the HP-PRRSV HuN4-F5-infected group were also significantly decreased compared to those in the uninfected group. However, there was no significant difference in the expression of proteasome subunits PSMB5, PSMB6, and PSMB7 between HP-PRRSV HuN4-F5-infected and uninfected groups. This study provides insight into the mechanisms underlying immune regulation by HP-PRRSV; specifically, this virus affects the antigen-processing machinery by suppressing IFN-γ-induced i-proteasome expression in infected AMs.