Experimental Study on the Anti-HP-PRRSV Effect of Manganese Ion-Mediated NF-κB Signaling Pathway

The precise antiviral mechanism of manganese ions (Mn²⁺) remains incompletely understood. In this study, we elucidated how Mn²⁺ counteracts highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) infection and defined its link to the NF-κB signaling pathway. First, we determined that 10 µM MnCl₂ was the maximum non-toxic dose on Marc-145 cells. Pretreatment with MnCl₂ at this dose before HP-PRRSV infection significantly inhibited viral replication, as evidenced by reduced viral titers and viral N protein expression, while also alleviating cytopathic effects and downregulating the secretion of pro-inflammatory cytokines IL-6 and IL-8. Mechanistically, HP-PRRSV infection suppressed the activation of the NF-κB pathway, indicated by decreased phosphorylation levels of p65 and IκBα. MnCl₂ pretreatment effectively reversed this suppression. Furthermore, it concurrently upregulated the expression of antiviral interferons, IFN-α and IFN-β. Crucially, functional validation using the specific NF-κB agonist Diproqualone (Dip-1) mimicked the antiviral effect of Mn²⁺, whereas inhibition of the pathway with BAY 11-7082 exacerbated infection and suppressed interferon production. Collectively, these findings demonstrate that manganese antagonizes HP-PRRSV infection by activating the NF-κB signaling pathway, which in turn induces a potent interferon response.