Proteome analysis of bronchoalveolar lavage from calves infected with bovine respiratory syncytial virus-Insights in pathogenesis and perspectives for new treatments.

Proteome analysis of bronchoalveolar lavage from calves infected with bovine respiratory syncytial virus-Insights in pathogenesis and perspectives for new treatments.
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DOI:
10.1371/journal.pone.0186594
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发表时间:
2017
期刊:
影响因子:
3.7
通讯作者:
Valarcher JF
Valarcher JF
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Hägglund S;Blodörn K;Näslund K;Vargmar K;Lind SB;Mi J;Araínga M;Riffault S;Taylor G;Pringle J;Valarcher JF

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人和牛呼吸道合胞病毒(HRSV/BRSV)分别是引起儿童和小牛严重下呼吸道感染的主要原因。这些病毒具有共同的流行病学、临床、病理学和遗传学特征,这使得比较研究具有很高的相关性。为了表征宿主对BRSV感染的反应,用串联质谱仪分析了未接种、感染BRSV、感染BRSV和未感染BRSV的小牛的支气管肺泡灌洗液(BAL)。蛋白质半定量,免疫印迹法检测蛋白质表达。对所选蛋白与病理、临床症状和病毒脱落的相关性进行了研究。患有BRSV引起的疾病的犊牛在BAL中发现总蛋白浓度增加,蛋白质数量减少。蛋白质谱的特征是中性粒细胞激活和已识别的抗氧化酶减少。肺泡间隔中性粒细胞的存在、中性粒细胞相关蛋白或抗氧化蛋白的表达水平以及LZTFL1与疾病密切相关。瓜氨酸组蛋白3是细胞外陷阱(ETS)的指示物,仅在未接种疫苗的BRSV感染动物中检测到。过度的中性粒细胞反应可能会导致呼吸道合胞病毒(RSV)诱导的疾病加重,导致体内活性氧的释放和解毒失衡,从而产生内毒素并引起弹性蛋白的降解。应进一步探索减轻中性粒细胞或抗氧化的治疗方法。
Human and bovine respiratory syncytial viruses (HRSV/BRSV) are major causes of severe lower respiratory tract infections in children and calves, respectively. Shared epidemiological, clinical, pathological and genetic characteristics of these viruses make comparative research highly relevant. To characterise the host response against BRSV infection, bronchoalveolar lavage supernatant (BAL) from i) non-vaccinated, BRSV-infected ii) vaccinated, BRSV-infected and iii) non-infected calves was analysed by tandem mass spectrometry. Proteins were semi-quantified and protein expression was validated by immunoblotting. Correlations between selected proteins and pathology, clinical signs and virus shedding were investigated. Calves with BRSV-induced disease had increased total protein concentrations and a decreased number of proteins identified in BAL. The protein profile was characterised by neutrophil activation and a reduction in identified antioxidant enzymes. The presence of neutrophils in alveolar septa, the expression level of neutrophil-related or antioxidant proteins and LZTFL1 correlated significantly with disease. Citrullinated histone 3, an indicator of extracellular traps (ETs), was only detected in non-vaccinated, BRSV-infected animals. By bringing disequilibrium in the release and detoxification of reactive oxygen species, generating ETs and causing elastine degradation, exaggerated neutrophil responses might exacerbate RSV-induced disease. Neutrophil-mitigating or antioxidant treatments should be further explored.
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