中文摘要：研究测定了感染猪IAV（H1N2）不同时间段（1天、3天和14天）后，猪肺部微小RNA（miRNAs）基因及蛋白的表达情况。研究发现了5种miRNAs是识别病毒性抗原和细胞凋亡的重要调节因子，其中4种miRNAs为已有报道过的，1种为新发现的。感染14天后，检测到11种不同表达的miRNAs。结果表明，miRNAs在急性感染期及其后期均起到重要作用，从而影响IAV感染后猪肺部的病变及肺部二次感染的易感性。
 
外文摘要：The innate immune system is paramount in the response to and clearance of influenza A virus (IAV) infection in non-immune individuals. Known factors include type I and III interferons and antiviral pathogen recognition receptors, and the cascades of antiviral and pro- and anti-inflammatory gene expression they induce. MicroRNAs (miRNAs) are increasingly recognized to participate in post-transcriptional modulation of these responses, but the temporal dynamics of how these players of the antiviral innate immune response collaborate to combat infection remain poorly characterized. We quantified the expression of miRNAs and protein coding genes in the lungs of pigs 1, 3, and 14 days after challenge with swine IAV (H1N2). Through RT-qPCR we observed a 400-fold relative increase in IFN-lambda 3 gene expression on day 1 after challenge, and a strong interferon-mediated antiviral response was observed on days 1 and 3 accompanied by up-regulation of genes related to the pro-inflammatory response and apoptosis. Using small RNA sequencing and qPCR validation we found 27 miRNAs that were differentially expressed after challenge, with the highest number of regulated miRNAs observed on day 3. In contrast, the number of protein coding genes found to be regulated due to IAV infection peaked on day 1. Pulmonary miRNAs may thus be aimed at fine-tuning the initial rapid inflammatory response after IAV infection. Specifically, we found five miRNAs (ssc-miR-15a, ssc-miR-18a, ssc-miR-21, ssc-miR-29b, and hsa-miR-590-3p)-four known porcine miRNAs and one novel porcine miRNA candidate-to be potential modulators of viral pathogen recognition and apoptosis. A total of 11 miRNAs remained differentially expressed 14 days after challenge, at which point the infection had cleared. In conclusion, the results suggested a role for miRNAs both during acute infection as well as later, with the potential to influence lung homeostasis and susceptibility to secondary infections in the lungs of pigs after IAV infection.
 
外文关键词：VIRUS-INFECTION; ANTIVIRAL PROTECTION; C-ELEGANS; SWINE; EXPRESSION; MODEL; GENES; HOST; LUNG; DISEASES
作者：Brogaard, L; Larsen, LE; Heegaard, PMH; Anthon, C; Gorodkin, J; Durrwald, R; Skovgaard, K
作者单位：丹麦技术大学
期刊名称：PLOS ONE
期刊影响因子：2.806
出版年份：2018
出版刊次：4
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