Porcine reproductive and respiratory syndrome virus (PRRSV) suppresses the anti-viral immune response of type I interferon (IFN) cytokines. This is a key contributor to the ability of PRRSV to persist in swine. This study examined the suppression of IFN-[alpha] 'in vitro' and the mechanism by which this occurs. By conventional RT-PCR and quantitative real-time RT-PCR, IFN-[alpha] mRNA appeared to be diminished during PRRSV infection of Marc-145 cells. Based on observations in the Marc-145 cell system, examination of IFN transcription factor interferon regulatory factor 3 (IRF-3) by luciferase reporter assay, immunofluorescence, and Western blot indicated that activation of IRF-3 did not appear to occur in cells infected with PRRSV. It was also found that PRRSV N protein had a negative effect on IRF-3 activation in HeLa cells. IRF-3 is an essential transcription factor for type I IFN expression and PRRSV may suppress the innate immune response through deactivation of IRF-3.