Taken together, these results indicate that SAMHD1 expression is upregulated by HP-PRRSV in the infection of PAMs, which is different from what was observed in MARC-145 cells, and type I IFN production is not required for the induction of SAMHD1 expression in porcine macrophages infected with HP-PRRSV. Here, SAMHD1 is linked to infection.