MiR-24-3p Promotes Porcine Reproductive And Respiratory Syndrome Virus Replication Through Suppression Of Heme Oxygenase-1 Expression

Porcine reproductive and respiratory syndrome virus(PRRSV) is one of the most economically important viruses affecting the swine industry worldwide. Our previous research showed that PRRSV down-regulates the expression of heme oxygenase-1(HO-1), a pivotal cytoprotective enzyme, post-infection and overexpression of HO-1 inhibits PRRSV replication. MicroRNAs regulate gene expression at the posttranscriptional level and have recently been demonstrated to play vital roles in pathogen-host interactions. The present study sought to determine whether microRNAs modulate HO-1 expression and by doing so regulate PRRSV replication. Using bioinformatic prediction and experimental verification, we demonstrate that HO-1 expression is regulated by miR-24-3p. A direct interaction between mi R-24-3p and HO-1 mRNA was confirmed using a number of approaches. Overexpression of miR-24-3p significantly decreased HO-1 mRNA and protein levels. Treatment of cells with protoporphyrin IX cobalt chloride(CoPP), a classical inducer of HO-1 expression, lead to decreased miR-24-3p expression, indicating that there is an inverse correlation between expression of miR-24-3p and HO-1 expression. In addition we observed that PRRSV infection induced miR-24-3p expression to facilitate viral replication. The suppressive effect of HO-1 induction by CoPP on PRRSV replication in Marc-145 cells and primary porcine alveolar macrophages could also be reversed by overexpression of miR-24-3p. Collectively, these results suggested that miR-24-3p promotes PRRSV replication through suppression of HO-1 expression, which not only provides new insights into virus-host interactions during PRRSV infection, but also suggests potential therapies for PRRSV infection.