Title: Impact of Porcine Arterivirus, Influenza B, and Their Coinfection on Antiviral Response in the Porcine Lung

Abstract

Interferon (IFN) cytokines induce an 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 four treatment groups: control, porcine reproductive and respiratory syndrome virus (PRRSV, also known as porcine arterivirus) 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 IBVmore » group had (n = 64) total DEGs across 3 and 5 dpi. Expression data were considered statistically significant based on false discovery rate (FDR) ≤ 0.1. Venn diagram comparisons of the DEGs across dpi showed that 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 Kyoto Encyclopedia of Genes and Genomes (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. Moreover, all infected groups showed prolonged upregulation in neutrophil degranulation pathway activity, possibly exacerbating symptomatic lung lesion pathology seen in these respiratory infections.« less

Authors:

Fleming, Damarius S. ^[1]; Miller, Laura C. ^[2]; Tian, Yun ^[3]; Li, Yonghai ^[4]; Ma, Wenjun  ^[5];

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• Search DOE PAGES for ORCID "0000-0003-0395-9404"

Sang, Yongming  ^[6]

• Search DOE PAGES for author "Sang, Yongming"
• Search DOE PAGES for ORCID "0000-0002-2980-2854"

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+ Show Author Affiliations

1. Oak Ridge Inst. for Science and Education (ORISE), Oak Ridge, TN (United States); US Dept. of Agriculture (USDA), Ames, IA (United States). National Animal Disease Center. Virus and Prion Research Unit
2. US Dept. of Agriculture (USDA), Ames, IA (United States). National Animal Disease Center. Virus and Prion Research Unit
3. Tennessee State Univ., Nashville, TN (United States). Dept. of Agricultural and Environmental Sciences
4. Kansas State Univ., Manhattan, KS (United States). Dept. of Diagnostic Medicine and Pathobiology
5. Kansas State Univ., Manhattan, KS (United States). Dept. of Diagnostic Medicine and Pathobiology; Univ. of Missouri, Columbia, MO (United States). Dept. of Molecular Microbiology and Immunology. Dept. of Veterinary Pathobiology
6. Tennessee State Univ., Nashville, TN (United States). Dept. of Agricultural and Environmental Sciences

Publication Date:

Wed Nov 11 00:00:00 EST 2020

Research Org.:

Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

Sponsoring Org.:

USDOE Office of Science (SC); USDA; National Science Foundation (NSF); National Institutes of Health (NIH)

OSTI Identifier:

1787231

Grant/Contract Number:  

AC05-00OR22725; AC05-06OR23100; 2018-67016-28313; IOS-1831988; R21AI1221906

Resource Type:

Accepted Manuscript

Journal Name:

Pathogens

Additional Journal Information:

Journal Volume: 9; Journal Issue: 11; Journal ID: ISSN 2076-0817

Publisher:

MDPI

Country of Publication:

United States

Language:

English

Subject:

59 BASIC BIOLOGICAL SCIENCES; PRRSV; IBV-S; lung; immune response; differential expression