Impact of Porcine Arterivirus, Influenza B, and Their Coinfection on Antiviral Response in the Porcine Lung.
Impact of Porcine Arterivirus, Influenza B, and Their Coinfection on Antiviral Response in the Porcine Lung.
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DOI：
10.3390/pathogens9110934
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发表时间：
2020-11-11
期刊：
影响因子：
--
通讯作者：
Sang Y
中科院分区：
文献类型：
--
作者：
Fleming DS;Miller LC;Tian Y;Li Y;Ma W;Sang Y
干扰素（IFN）细胞因子在感染部位的细胞中诱导自主抗病毒状态，以限制病毒传播并严格调节整体抗病毒反应。抗病毒状态通过表达数百种IFN刺激的基因导致宿主保护，这些基因通过多种机制限制病毒感染，例如，直接通过病毒基因组降解和间接通过细胞代谢抑制。将幼猪分成四个处理组：对照组、猪繁殖与呼吸综合征病毒（PRRSV，也称为猪动脉炎病毒）感染组、流感B病毒（IBV）感染组和IBV/PRRSV共感染组。对于对照、PRRSV和IBV/PRRSV共感染，在感染后（dpi）3、5和7天收集肺组织，对于IBV，在感染后3和5天收集肺组织。使用usegalaxy.org工具，针对S.scrofa 11.1参考基因组进行转录组学分析。基于模型处理+ dpi +处理：dpi + E，使用DeSeq 2进行差异表达基因（DEG）分析。下游分析检查了DEG在每个dpi的相互作用，用于过度富集的基因本体（G. O.）条件和途径。感染组与对照组的比较在所有时间点产生了PRRSV组的总DEG（n = 1412）和IBV/PRRSV组的总DEG（n = 1578）。IBV组在3和5 dpi时具有（n = 64）总DEG。基于错误发现率（FDR）≥ 0.1，认为表达数据具有统计学显著性。不同dpi的DEG维恩图比较显示，在3 dpi时，各组仅共享16个DEG，在5 dpi时没有共享DEG，而在7 dpi时，仅比较了PRRSV和IBV/PRRSV组，并共享总共43个DEG。在比较中，在抗病毒基因如IRF 1、MX 1和OAS 2中观察到差异表达。IBV组和IBV/PRRSV组在感染后早期抗病毒基因的表达量高于PRRSV组。此外，来自比较的下调基因聚集在影响肺发育和细胞完整性的京都基因和基因组百科全书（KEGG）途径周围。在IBV感染过程中，宿主IFN和抗病毒基因的早期表达可能导致病毒RNA降解、组装和转录抑制。相比之下，PRRSV组中抗病毒基因的表达随时间推移而下降。这种减少可以解释为什么PRRSV感染持续存在，而IBV清除。此外，所有感染组均显示中性粒细胞脱颗粒途径活性延长上调，可能加剧这些呼吸道感染中观察到的症状性肺部病变病理学。
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 IBV 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.
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