Infection with Classical Swine Fever Virus Induces Expression of Type III Interferons and Activates Innate Immune Signaling

Abstract

Classical swine fever virus (CSFV) commonly infects the lymphatic tissues and immune cells of pigs and could cause a lethal disease in the animals. The process and release of cytokines like type III interferons (IFNs) is one of the important responses of the host innate immunity to viral infection. However, little information is available about type III IFN response to the CSFV infection. In this study, we investigated the expression of type III IFNs including interleukin-28B (IL-28B) and IL-29 in PK-15 cells and pigs following CSFV infection. We found that infection with CSFV was able to induce expression of IL-28B and IL-29 in PK-15 cells, although the increased levels of type III IFNs were limited. Importantly, up-regulation of IL-28B and IL-29 was further observed in CSFV infected animal tissues. The production of IL-28B and IL-29 was reduced by the inactivation of NF-κB in cells, indicating that activated NF-κB is required for efficient expression of type III IFNs induced by CSFV. Moreover, our experiments demonstrated that infection with CSFV strongly stimulated the downstream of STAT1 signaling in vitro and in vivo. In addition, several critical IFN-stimulated genes (ISGs) including IFITM3, OASL, OAS1, and ISG15 were significantly upregulated at both mRNA and protein levels in PK-15 cells and infected pigs. Together, these results reveal that CSFV can trigger host antiviral immune responses including production of type III IFNs, activation of STAT1, and induction of some critical ISGs.

MG132 Attenuates the Replication of Classical Swine Fever Virus in vitro

“…Upon sensing CSFV infection, cytokines are released followed by transcription of a series of ISGs induced by the activation of the JAK-STAT pathway. A previous study has confirmed the critical roles of type III interferons in the activation of the JAK-STAT pathway in CSFV-infected cells (Cai et al, 2017). In our study, significant innate immune molecules related to viral infection including IFN-α and three ISGs are examined.…”

Head Start Immunity: Characterizing the Early Protection of C Strain Vaccine Against Subsequent Classical Swine Fever Virus Infection

“…Expression of the ISG15 gene has previously been shown to be induced in response to virulent strains of CSFV in vitro (45, 46). However, this is the first study to demonstrate induction of the ISG15 pathway in response to vaccination with C strain in vivo and specifically that this induction occurs in the tonsil, the primary site of CSFV replication.…”

Global Mapping of H3K4 Trimethylation (H3K4me3) and Transcriptome Analysis Reveal Genes Involved in the Response to Epidemic Diarrhea Virus Infections in Pigs

“…In addition, previous epidemiological studies have revealed the associations of SNPs in the human OASL gene with altered susceptibility to West Nile and hepatitis C virus infections [35,36]. The OASL gene has also been shown to be obviously up-regulated in response to porcine virus infections such as swine influenza virus and fever virus [37,38]. In addition, our comparative analysis identified other genes related to host-pathogen interactions such as ISG15 that is an antiviral molecule with activity against both DNA and RNA viruses [39] and AGR2 that regulates the production of intestinal mucus [40].…”