Impact of porcine arterivirus, influenza B, and their coinfection on antiviral response in the porcine lung

Authors: FLEMING, DAMARIUS - Orise Fellow; Miller, Laura; TIAN, YUN - Tennessee State University; LI, YONGHAI - Kansas State University; MA, WENJUN - Kansas State University; SANG, YONGMING - Tennessee State University

Submitted to: Pathogens
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/27/2020
Publication Date: 11/11/2020
Citation: Fleming, D.S., Miller, L.C., Tian, Y., Li, Y., Ma, W., Sang, Y. 2020. Impact of porcine arterivirus, influenza B, and their coinfection on antiviral response in the porcine lung. Pathogens. 9(11). Article 9110934. https://doi.org/10.3390/pathogens9110934.
DOI: https://doi.org/10.3390/pathogens9110934

Interpretive Summary: Respiratory illnesses on in livestock farms represents a source of economic and production losses that affect food safety. Additionally, this can also pose a health risk to animal workers in close contact with infected livestock. For swine producers these illnesses can sometimes be the product of coinfections such as PRRSV, which only harms swine, and influenza B which can cause illness in swine and humans. The purpose of the current study was to determine the severity of the coinfection and what parts of the swine immune system responded to the coinfection. What was found is that swine mount an immune response to PRRSV and PRRSV/ influenza B coinfections that initiate recovery but possibly plays a role in lung injury. The results also demonstrated that swine immune response will clear influenza B infections within a few days. The study results give insight into the ability of the swine immune system to deal with multiple respiratory infections which opens up new avenues for finding treatments. The study also indicates that the swine immune system clears influenza B infections quickly, minimizing the chance of infection in livestock workers.

Technical Abstract: Interferon (IFN) cytokines induce autonomous antiviral state in cells of the infected site to restrict virus spreading and critically regulate overall antiviral response. The antiviral state leads to host protection through expression of hundreds of IFN-stimulated genes that restrict viral infection through multiple mechanisms; for example directly in viral genome degradation and indirectly through cellular metabolic inhibition. Young pigs were split into 4 treatment groups: control, porcine reproductive and respiratory syndrome virus (PRRSV) infected, influenza B virus (IBV) infected, and IBV/PRRSV coinfection. Lung tissue was collected at 3, 5, and 7 days post infection (dpi) for control, PRRSV and IBV/PRRSV coinfection, and at 3 and 5 dpi for IBV. Transcriptomic analysis, using usegalaxy.org tools, was performed against the S.scrofa 11.1 reference genome. Differentially expressed gene (DEG) analysis was carried out using DeSeq2 based on the model treatment + dpi + treatment:dpi + E. Downstream analysis examined the interaction of DEG at each dpi for over-enriched gene ontology (G.O.) terms and pathways. Comparisons of the infected groups vs the controls yielded a total of (N=1412) DEGs for the PRRSV group and (N=1578) for the IBV/PRRSV group across all timepoints. The IBV group had (N=64) total DEGs across 3 and 5 dpi. Expression data was considered statistically significant based on FDR ' 0.1. Venn diagram comparisons of the DEGs across dpi showed groups shared only 16 DEGs at 3 dpi, no DEGs were shared at 5 dpi, and for 7 dpi, only the PRRSV and IBV/PRRSV groups were compared and shared a total of 43 DEGs. Across the comparisons differential expression was observed in antiviral genes such as IRF1, MX1, and OAS2. The IBV and IBV/PRRSV groups showed higher expression of antiviral genes at earlier dpi than the PRRSV group. Additionally downregulated genes from the comparisons clustered around KEGG pathways effecting lung development and cellular integrity. Early expression of host IFN and antiviral genes may lead to viral RNA degradation, and assembly and transcription inhibition in the IBV infections. In comparison, expression of antiviral genes in the PRRSV group decreased across time. The decrease may explain why PRRSV infections persist, while IBV clears. Also, all infected groups showed prolonged upregulation in neutrophil degranulation pathway activity, possibly exacerbating symptomatic lung lesion pathology seen in these respiratory infections.