Interactions of porcine reproductive and respiratory syndrome virus with innate immune responses

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] North American field isolates of PRRSV differed in their type I IFN response with respect to induction, sensitivity and suppression. Furthermore, one PRRSV isolate strongly enhanced polyI:C - induced IFN-[alpha] production in PAM cultures and this priming effect was suppressed by other PRRSV isolates. PRRSV activates NF-[kappa]B which is a critical regulator of innate and adaptive immune function. NF-[kappa]B activation was dependent on virus replication and I[kappa]B[alpha] degradation. ROS production was involved in NF-[kappa]B activation by PRRSV. NF-[kappa]B dependent expression of MMP-2 and MMP-9 suggested a possible role of the NF-[kappa]B pathway in PRRSV pathogenesis and the immune response. PRRSV infection induced both intrinsic and extrinsic apoptosis pathways and linked these two pathways via Bid cleavage by caspase-8. While apoptosis was significantly suppressed by caspase inhibitors, the same inhibitors did not affect PRRSV replication. This study also provided evidence of a possible involvement of NF-[kappa]B and ROS in apoptosis induced by PRRSV.