Taken together, these results demonstrate that PMLIV has a dual effect on viral infection: (i) an early intrinsic anti-VSV activity that was not eradicated by treatment with anti-IFNAR1 mAb, knockdown of STAT1 or IRF3 and (ii) an activation of innate immune signaling that occurs later and leads to the production and the secretion of type I IFN, which can protect other cells from viral infection. Here, IFNAR1 is linked to viral infectious disease.