Inhibition of African Swine Fever Virus Replication by Porcine Type I and Type II Interferons

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 (10 5 U/kg) recombinant porcine IFNs (PoIFN-α and PoIFN-γ) significantly reduced viral load compared to that with high-dose (10 6 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.

Lactobacillus plantarum surface-displayed ASFV (p54) with porcine IL-21 generally stimulates protective immune responses in mice

“…Protective immunity against African classical swine fever virus is lost when CD8 + T lymphocytes are depleted in the body (Oura et al 2005 ). Some studies have shown that interferon-γ can inhibit the replication of African classical swine fever virus (Fan et al 2020 ), and T cells proliferate and increase the secretion of interferon-γ in mice immunized with ASFV structural protein (Chen et al 2016 ). Interestingly, in our study, we also found that the number of activated CD4 + T cells and CD8 + T cells in the experimental group increased, the secretion of IFN-γ in CD4 + and CD8 + T cells increased, and lymphocytes proliferated under stimulation with the ASFV p54 antigen.…”

Baculovirus Vectors Induce the Production of Interferons in Swine: Their Potential in the Development of Antiviral Strategies

“…Among the many strategies studied to rapidly contain outbreaks caused by highly contagious viruses in pigs, the administration or expression of porcine IFN-α [17,62,63], β [15], γ [9,14], or λ [16] or the use of some TLR ligands like poly I:C [64] have been some of the most successful ones. On the other hand, the intramuscular inoculation of CpG ODNs, which are TLR-9 ligands, failed in providing protection in pigs against a challenge with FMDV 2 days after inoculation [65].…”

“…Interferons (IFNs), the main antiviral soluble factors of innate immunity, have been thoroughly studied and even used for the treatment of several human and animal viral diseases [3][4][5][6]. Although their direct use in swine and other livestock animals is not profitable, IFN-based antiviral strategies could be promising against epidemic IFN-sensitive viruses like porcine reproductive and respiratory syndrome virus [7], porcine epidemic diarrhea virus [8], African swine fever virus [9], and influenza virus [10,11].…”

Inhibition of BET family proteins suppresses African swine fever virus infection

“…At present, the research and development of anti-ASFV drugs mainly focuses on two categories: (1) inhibitors that directly act on the proteins encoded by AFSV to affect its replication and (2) inhibitors that act on host protein factors required for viral replication to indirectly exert an anti-ASFV effect (25). Antiviral agents against ASFV currently include interferon (26), antibiotics (27), nucleoside analogues (28), plant-derived products (29) and other compounds that have been reported to inhibit ASFV replication (25). However, the safety of action of these antiviral drugs has not been studied in depth.…”