Oxidative stress induces porcine RCAN1-1L to promote mitophagy and enhance PRRSV replication.
TL;DR
It is revealed that the glycoprotein 5 of PRRSV induced the porcine RCAN1-1L isoform through oxidative stress and the findings demonstrate that RCAN1-1L links mitophagy to PRRSV pathogenesis and serves as a potential antiviral therapeutic target.
Abstract
Porcine reproductive and respiratory syndrome virus (PRRSV) causes mitochondrial dysfunction and induces mitophagy to facilitate virus replication. The regulator of calcineurin 1 (RCAN1) is a biomarker of oxidative stress caused by mitochondrial dysfunction. However, whether RCAN1 is involved in PRRSV pathogenesis remains unclear. In this study, we reveal that the glycoprotein 5 (GP5) of PRRSV induced the porcine RCAN1-1L isoform through oxidative stress. Overexpression of RCAN1-1L was found to significantly promote PRRSV proliferation in PK15CD163 cells. Transcriptome analysis of PRRSV-infected PK15CD163 cells transfected with siRNA targeting RCAN1-1L identified 62 differentially expressed genes, most of which were associated with mitochondrial functions. Furthermore, RCAN1-1L downregulated the expression of the mitochondrial outer membrane protein TOM20 while upregulating the mitophagy-associated proteins PINK1 and the autophagosome marker LC3II. The accumulation of lysosomes acidified mitochondria and enhanced mitophagic flux were observed following the overexpression of RCAN1-1L during PRRSV infection. In addition, RCAN1-1L decreases intracellular ROS levels and downregulates the expression of the apoptotic marker cleaved Caspase-3 in PRRSV infected cells. The findings demonstrate that RCAN1-1L links mitophagy to PRRSV pathogenesis and serves as a potential antiviral therapeutic target.