Inhibition of porcine reproductive and respiratory syndrome virus by interferon-gamma and recovery of virus replication with 2-aminopurine

Porcine reproductive and respiratory syndrome virus (PRRSV) belongs to a gr oup of RNA viruses that establish persistent infections. A proposed strateg y for evading immunity during persistent PRRSV infection is by preventing t he induction of IFN activity in pigs and/or by blocking the activation of a ntiviral proteins in permissive cells. IFN-gamma mRNA expression was observ ed in the lymph nodes and lungs of pigs infected with wild-type PRRSV strai n SDSU-23983. Pretreatment of MARC-145 cells with IFN-gamma inhibited wild- type (SDSU-23983 P6) and culture-adapted (SDSU-23983 P136) PRRS viruses in a dose-dependent manner and at relatively low concentrations. The effect of IFN-gamma on virus replication included reductions in the number of infect ed cells, virus yield, and RNA content in single cells. Virus replication w as partially restored by the addition of 2-aminopurine (2-AP), an inhibitor of dsRNA inducible protein kinase (PKR). The addition of 2-AP also restore d the viral RNA content per cell to near normal levels, suggesting that inh ibition of viral RNA synthesis was through PKR. The principal difference be tween P6 and P136 isolates was the recovery of P136 replication with lower concentrations of 2-AP. Immunostaining with anti-PKR antibody showed a redi stribution of PKR from the cytoplasm into nucleoli of infected cells.