Porcine reproductive and respiratory syndrome virus activates the transcription of interferon alpha/beta (IFN-α/β) in monocyte-derived dendritic cells (Mo-DC)

Zhang, Hanmo; Guo, Xueshui; Nelson, Eric; Christopher-Hennings, Jane; Wang, Xiuqing

Porcine reproductive and respiratory syndrome virus (PRRSV) is known to be a poor inducer of interferon alpha/beta (IFN-α/β), which may contribute to the delayed development of adaptive immunity and the resultant viral persistence. However, the exact mechanism by which PRRSV inhibits the induction of IFN-α/β during infection of its natural host cells remains less well defined. Here, we show that PRRSV efficiently activates the transcription of IFN-α/β in porcine monocyte-derived dendritic cells (Mo-DC) in a time-dependent and transient manner; and this effect is dependent on the activation of phosphatidylinositol 3-kinase (PI3K). Despite the abundant IFN-α transcripts detected in PRRSV-infected Mo-DC, little or no detectable IFN-α is found in the supernatants and cell lysates of PRRSV-infected Mo-DC, suggesting that PRRSV either blocks the translation of IFN-α or inhibits the RNA processing and transport. Furthermore, we observed that PRRSV infection significantly reduced the induction of IFN-α by Poly I:C treatment; and virus replication is essential to the effect since heat-inactivated PRRSV has no effect on IFN-α induction by Poly I:C. Overall, our data provide evidence for the possible role of PI3K in the activation of the transcription of IFN-α/β by PRRSV. We conclude that PRRSV inhibits the induction of IFN-α in Mo-DC by as yet undefined post-transcriptional mechanisms.