Antiviral activity of porcine interferon omega 7 against foot-and-mouth disease virus in vitro.

Foot-and-mouth disease (FMD) is a disease of worldwide economic importance, and vaccines play an important role in preventing FMDV outbreaks. However, new control strategies are still needed since FMDV outbreaks still occur in some disease-free countries. Currently, interferon (IFN)-based strategies have been demonstrated to be an efficient biotherapeutic option against FMDV; however, interferon omega (IFN-ω) has not yet been assessed in this capacity. Thus, this study evaluated the antiviral activity of porcine IFN omega 7 (PoIFN-ω7) against FMDV. After the PoIFN-ω7 was expressed and purified, cell proliferation assays and quantitative real-time reverse transciption-polymerase chain reaction were used to evaluate the effective anti-cytopathic concentration of PoIFN-ω7 and its effectiveness pre- and post-infection with FMDV in swine kidney cells (IBRS-2). Results showed the rHis-PoIFN-ω7 fusion protein was considerably expressed using Escherichia coli BL21 (DE3) strain, and the recombinant protein exhibited significant in vitro protection against FMDV, including two strains belonging to type O and A FMDV, respectively. In addition, PoIFN-ω7 upregulated the transcription of Mx1, ISG15, OAS1, and PKR genes. These findings indicated that IFN-ω has the potential for serving as a useful therapeutic agent to prevent FMDV or other viral outbreaks in pigs.

Inhibitory effects of homoharringtonine on foot and mouth disease virus in vitro.

Foot-and-mouth disease (FMD) is a highly contagious disease that affects cloven-hoof animals including cattle, swine, sheep, goats, and lots of wild species. Effectively control measures are urged needed. Here, we showed that homoharringtonine treatment exhibited a strong inhibitory effect against two different strains of FMDVs (O/MYA98/BY/2010 and A/GD/MM/2013) in swine kidney (IBRS-2) cells. Further experiments demonstrated that homoharringtonine did not affect virus attachment or entry. Using time-of-addition assays, we found that the antiviral activity of homoharringtonine occurred primarily during the early stage of infection. These results demonstrated that homoharringtonine might be an effective anti-FMDV drug. Further studies are required to explore the antiviral activity of homoharringtonine against FMDV replication in vivo.

A novel type I interferon, interferon alphaomega, shows antiviral activity against foot-and-mouth disease virus in vitro.

Recently, a novel type I interferon alphaomega (IFN-αω), also known as IFN-µ, was identified. However, the biological activity of IFN-αω remain poorly understood. In this study, the porcine IFN-αω (PoIFN-αω) was expressed, purified, and its antiviral activities assessed by its ability to inhibit the cytopathic effect caused by FMDV on IBRS-2 cells. In addition, q-PCR was used to evaluate the expression of IFN-stimulated genes induced by PoIFN-αω. It was found that PoIFN-αω exerted effective antiviral activity against FMDV pre- and post-infection. Additionally, PoIFN-αω induced the transcription of IFN-stimulated genes, including Mx1, ISG15, OAS1, and PKR genes. Our study reported a new indication of PoIFN-αω as an effective anti-FMDV agent for the first time.

Lithium chloride inhibits early stages of foot-and-mouth disease virus (FMDV) replication in vitro.

Foot-and-mouth disease virus (FMDV) causes an economically important and highly contagious disease of cloven-hoofed animals such as cattle, swine, and sheep. FMD vaccine is the traditional way to protect against the disease, which can greatly reduce its occurrence. However, the use of FMD vaccines to protect early infection is limited. Therefore, the alternative strategy of applying antiviral agents is required to control the spread of FMDV in outbreak situations. As previously reported, LiCl has obviously inhibition effects on a variety of viruses such as transmissible gastroenteritis virus (TGEV), infectious bronchitis coronavirus (IBV), and pseudorabies herpesvirus and EV-A71 virus. In this study, our findings were the first to demonstrate that LiCl inhibition of the FMDV replication. In this study, BHK-21 cell was dose-dependent with LiCl at various stages of FMDV. Virus titration assay was calculated by the 50% tissue culture infected dose (TCID50 ) with the Reed and Muench method. The cytotoxicity assay of LiCl was performed by the CCK8 kit. The expression level of viral mRNA was measured by RT-qPCR. The results revealed LiCl can inhibit FMDV replication, but it cannot affect FMDV attachment stage and entry stage in the course of FMDV life cycle. Further studies confirmed that the LiCl affect the replication stage of FMDV, especially the early stages of FMDV replication. So LiCl has potential as an effective anti-FMDV drug. Therefore, LiCl may be an effective drug for the control of FMDV. Based on that, the mechanism of the antiviral effect of LiCl on FMDV infection is need to in-depth research in vivo.

Antiviral activity of porcine interferon delta 8 against foot-and-mouth disease virus in vitro.

Foot-and-mouth disease (FMD) is one of the most devastating diseases affecting livestock. Since vaccines fail to provide protection until seven days post-vaccination, the application of anti-viral molecules is imperative for suppressing the spread of FMDV prior to development of an adaptive immune response. Interferons (IFNs) are effective for the host to fight FMDV infections; however, a novel type I IFNs, interferon delta (IFN-δ), has not been investigated for their antiviral effects against this virus. Thus, this study investigated FMDV infection, upon pre- and post-treatment with PoIFN-δ8. Real-time quantitative PCR was used to quantify the expression levels of IFN-stimulated genes (ISGs), including ISG15, OAS1, PKR, and Mx1. Results showed the PoIFN-δ8 lacking its signal sequence was efficiently expressed in Escherichia coli, and the purified recombinant PoIFN-δ8 exerted a significantly protective effect against two different serotypes of FMDV in IBRS-2 cells. In addition, PoIFN-δ8 induced the expression of IFN-stimulated genes. These findings highlight the significance of PoIFN-δ might serve as an antiviral agent for the prevention of FMDV in pigs and will stimulate the study of exploiting the potential biological functions of IFN-δ in the future.

Transcriptomic analysis of porcine PBMCs in response to FMDV infection.

Foot-and-mouth disease (FMD) is a significant zoonotic infectious disease. It has an important economic impact throughout the world. As well, it is a considerable threat to food security. At present, the molecular mechanism of FMDV infection is not clear to a large extent. Innate immune response is the first line of defense against infectious diseases. The systematic analysis of the host immune response to infection has an important role in understanding the pathogenesis of infection. However, there are few reports about effect of immune regulation on virus replication in the interaction of virus and host cellular. High-throughput RNA-seq technology as a powerful and efficient means for transcript analysis provides a new insight into FMDV study. In this study, RNA extracted from pig PBMCs infected with O subtype FMDV at 4 dpi. A total of 29942658 and 31452917 Illumina read pairs were obtained from the non-infected (NI) group and infected (I) group, respectively. The clean bases for all samples are 3.61G (NI group) and 3.79G (I group), respectively. The clean reads of the NI and I group that mapped to pig genome data were 47195073 (81.82%) and 46556714 (76.85%), respectively. Most of the clean reads were distributed in the exon region, followed by intron region and intergenic region. Differently expressed (DE) genes were analyzed using edgeR software. 451 genes were differentially expressed between the infected and the non-infected groups. According to the comparison analysis, more genes were down-regulated in the non-infected samples than in those infected with FMDV.66 out of 451 genes were down-regulated, 385 out of 451 genes were up-regulated following FMDV infection. For function classification and pathway analysis, among 17741 assembled unigenes, there are 349 genes which are different genes of GO notes. Moreover, 49 genes were down-regulated, 300 genes were up-regulated associate with GO term. 1621 were successfully annotated by GO assignments, belonging to one or more of the three categories: biological process, cellular component, and molecular function. According to KEGG analysis,the main pathway was represented including protein processing in endoplasmic reticulum, phagosome, cell cycle and cytokine-cytokine receptor interaction. Some key DE genes related to immune process and signaling pathways were analyzed and quantified by RT-PCR. This is the first systematical transcriptome analysis of pig PBMCs infected by FMDV. These findings will help us better understand the host Cell-FMDV interaction and its relationship to pathogenesis, as well as contribute to the prevention and control of FMDV.