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

Authors: Hau, Samantha; KELLNER, STEVEN - Non ARS Employee (USA) (only Use In Extenuating Circumstance); KNUDSEN, NICKOLAS - Ambrx Inc; SKIDMORE, LILLIAN - Ambrx Inc; CANNING, PETER - Elanco Animal Health, Inc; BROCKMEIER, SUSAN - Retired ARS Employee (USA)

Submitted to: Frontiers in Veterinary Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/23/2026
Publication Date: 9/3/2026
Citation: Hau, S.J., Kellner, S.G., Knudsen, N., Skidmore, L., Canning, P.C., Brockmeier, S.L. 2026. Porcine interferon-alpha but not interferon-lambda inhibits replication of genotypically diverse PRRSV isolates in vitro. Frontiers in Veterinary Science. https://doi.org/10.3389/fvets.2026.1873208.
DOI: https://doi.org/10.3389/fvets.2026.1873208

Interpretive Summary: Interferons (IFNs) are antiviral signals produced by host cells in response to viral infection. IFN signals cause cells to enter an antiviral state. These cells become more resistant to viral infection. Many viruses can interrupt this process. One such virus is Porcine Reproductive and Respiratory Syndrome virus (PRRSV). PRRSV reduces the host IFN response, which allows it to have a more productive infection. Prior research showed treatment with IFN products reduces disease severity, but the effect is not sustained over time. In this study, we tested two IFNs (IFN-alpha and IFN-lambda) for their ability to prevent PRRSV replication in vitro. IFN-alpha prevented replication of genetically diverse PRRSV isolates that show different pathogenicity in vivo. IFN-lambda did not reduce PRRSV replication. IFN-alpha caused increased transcription of IFN-inducible genes compared with IFN-lambda, leading to a stronger antiviral effect. Finally, we tested IFN-alpha following conjugated to polyethylene glycol (PEGylation). PEGylation extends the half life and increases the duration of activity of a single treatment. PEGylated IFN-alpha constructs reduced PRRSV replication. PEGylation makes IFN-alpha a more feasible product for field applications. This work provides a foundation for future animal work testing the use of PEGylated IFN products for treatment of swine viral diseases, including PRRSV.

Technical Abstract: 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. In this report, we evaluated the efficacy of pIFN-alpha (pIFNa) and pIFN-lambda (pIFN') at inhibiting PRRSV replication in porcine alveolar macrophages using a genotypically diverse subset of PRRSV isolates. pIFNa more efficiently inhibited PRRSV replication and induced greater transcription IFN-stimulated genes. Additionally, because the utility of many cytokine products in vivo is limited by half-life and dosing interval, we assessed PEGylated constructs of pIFNa for their capacity to inhibit PRRSV replication. PEGylated pIFNa reduced PRRSV replication in pretreated cells; however, the efficiency of inhibition was reduced compared to wild type pIFNa. This work indicates PEGylated pIFNa has potential as a biotherapeutic product to control PRRSV replication in pigs.