Abstract

Interferons (IFNs) are proteins produced by a variety of cells during the process of virus infection. It can activate the transcription of multiple functional genes in cells, regulate the synergistic effect of multiple signaling pathways, and mediate a variety of biological functions such as antiviral activity and immune regulation. The symptoms of hosts infected with African swine fever virus (ASFV) depend on the combined interaction between viruses and the host. However, it is unclear whether IFNs can be used as an emergency preventive treatment for ASFV. This study focused on the use of recombinant porcine IFNs, produced by Escherichia coli, to inhibit the replication of ASFV. The activity of IFN against ASFV was detected using primary alveolar macrophages at different doses through immunofluorescence assays and quantitative real-time PCR. We found that both 1000 and 100 U/mL doses significantly inhibited the replication of ASFV. Meanwhile, we found that IFNs could significantly trigger the production of a variety of IFN-induced genes (IFIT1, IFITM3, Mx-1, OASL, ISG15, PKR, GBP1, Viperin, BST2, IRF-1, and CXCL10) and MHC molecules, which play key roles in resistance to virus infection. Peripheral blood samples were also obtained from surviving pigs treated with IFNs, and the viral load was determined. Consistent with in vitro tests, low-dose (105 U/kg) recombinant porcine IFNs (PoIFN-α and PoIFN-γ) significantly reduced viral load compared to that with high-dose (106 U/kg) treatment. Our results suggest that recombinant porcine IFNs have high antiviral activity against ASFV, providing a new strategy for the prevention of African swine fever.

Highlights

  • African swine fever virus (ASFV) is an enveloped, icosahedral, double-stranded DNA virus that infects the macrophages of domestic swine (Galindo and Alonso, 2017)

  • We investigated the antiviral effect of recombinant porcine IFNs (PoIFN-α and PoIFN-γ) produced in Escherichia coli and their use as an emergency treatment for ASFV-positive pigs

  • The antiviral activities of PoIFNα and PoIFN-γ were determined according to the cytopathic effect (CPE) inhibition method based on the VSV/Porcine kidney 15 cells (PK15), VSV/MadinDarby bovine kidney cells (MDBK), and VSV/Madin-Darby Canine Kidney cells (MDCK) systems and according to previously described protocols (Armstrong, 1971; Taira et al, 2005)

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Summary

Introduction

African swine fever virus (ASFV) is an enveloped, icosahedral, double-stranded DNA virus that infects the macrophages of domestic swine (Galindo and Alonso, 2017). Inhibition of ASFV Replication by Interferons (ASF) is a highly contagious hemorrhagic viral disease of domestic and wild pigs (Sus scrofa; Yutin et al, 2009). It infects animals with a ≥90% mortality rate and causes serious economic and production losses worldwide (Parker et al, 1969; Thomson et al, 1980). Outbreaks of ASFV affect pork production and consumption, as well as the annual number of pigs slaughtered (Esparza et al, 1988)

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