Marked differences between MARC-145 cells and swine alveolar macrophages in IFNβ-induced activation of antiviral state against PRRSV

The activation of antiviral activity induced by recombinant swine interferon beta (rswIFNβ) against PRRSV was comparatively examined in MARC-145 cells and porcine alveolar macrophages (PAMs). A dose–response analysis showed, in MARC-145 cells, that isolate Mo25544 was highly sensitive to rswIFNβ while a vaccine strain and isolate PDV130-9301 were resistant to different extents. In contrast, all three viruses were equally sensitive to rswIFNβ in PAMs even at the lowest dose of IFN utilized in the bioassays. To analyze potential differences in mechanisms of antiviral activation between these cells, treatment with 2-aminopurine (2-AP), an inhibitor of double-stranded RNA-dependent protein kinase (PKR), was performed in rswIFNβ-treated cells. Addition of 2-AP to rswIFNβ-primed MARC-145 cells restored replication of the Mo25544 isolate, and to some extent that of vaccine virus and PDV130-9301. In contrast, virus replication could not be rescued for any of the three viruses with 2-AP in rswIFNβ-treated PAMs. The differences in sensitivity of PRRSV to rswIFNβ as well as the effects of 2-AP strongly suggest that MARC-145 cells and PAMs utilize different rswIFNβ-associated antiviral pathways. Therefore, studies to understand virus-host cell interactions performed in MARC-145 cells require additional scrutiny when utilized as a host cell model for immunologic responses to PRRSV.