Porcine interferon-alpha but not interferon-lambda inhibits replication of genotypically diverse PRRSV isolates in vitro.

INTRODUCTION: Porcine reproductive and respiratory syndrome (PRRS) is an economically devastating viral infection in pigs that results in estimated losses of $1.2 billion annually. Control of porcine reproductive and respiratory syndrome virus (PRRSV) has been challenging due to the weak and delayed development of adaptive immunity to the virus. This has been partially attributed to the low induction of host interferon (IFN). IFNs are cytokines that induce an antiviral state in target cells and promote the development of the adaptive immune response to the virus. The use of exogenous IFNs are of interest in the control of PRRSV in the swine industry. METHODS: The efficacy of porcine IFN-alpha (pIFNα) and porcine IFN-lambda (pIFNλ) at inhibiting PRRSV replication in porcine alveolar macrophages in vitro using a genotypically diverse subset of PRRSV isolates. Additionally, because the utility of many cytokine products in vivo is limited by half-life and dosing interval, PEGylated constructs of pIFNα were assessed for their capacity to inhibit PRRSV replication. RESULTS: Porcine IFNα more efficiently inhibited PRRSV replication and induced greater transcription of IFN-stimulated genes than pIFNλ; however, the efficacy of PRRSV inhibition was strain dependent. PEGylated pIFNα also reduced PRRSV replication in pretreated cells; however, the efficiency of inhibition was reduced compared to wild type pIFNα. DISCUSSION: Porcine IFNα was shown to be more capable of inhibiting PRRSV replication; however, some strains have reduced susceptibility to pIFN treatment. This work indicates PEGylated pIFNα retains functional activity and has potential as a biotherapeutic product to control PRRSV replication in pigs.