Acute experimental infection of bats and ferrets with Hendra virus: Insights into the early host response of the reservoir host and susceptible model species.,PLoS Pathogens

当前位置： X-MOL 学术 › PLOS Pathog. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Acute experimental infection of bats and ferrets with Hendra virus: Insights into the early host response of the reservoir host and susceptible model species.
PLoS Pathogens ( IF 5.5 ) Pub Date : 2020-03-30 , DOI: 10.1371/journal.ppat.1008412
Amanda P Woon _{1,

2} , Victoria Boyd ₃ , Shawn Todd ₃ , Ina Smith ₃ , Reuben Klein ₃ , Isaac B Woodhouse _{4,

5} , Sarah Riddell ₆ , Gary Crameri ₃ , John Bingham ₆ , Lin-Fa Wang ₇ , Anthony W Purcell ₁ , Deborah Middleton ₆ , Michelle L Baker ₃

Affiliation

Bats are the natural reservoir host for a number of zoonotic viruses, including Hendra virus (HeV) which causes severe clinical disease in humans and other susceptible hosts. Our understanding of the ability of bats to avoid clinical disease following infection with viruses such as HeV has come predominantly from in vitro studies focusing on innate immunity. Information on the early host response to infection in vivo is lacking and there is no comparative data on responses in bats compared with animals that succumb to disease. In this study, we examined the sites of HeV replication and the immune response of infected Australian black flying foxes and ferrets at 12, 36 and 60 hours post exposure (hpe). Viral antigen was detected at 60 hpe in bats and was confined to the lungs whereas in ferrets there was evidence of widespread viral RNA and antigen by 60 hpe. The mRNA expression of IFNs revealed antagonism of type I and III IFNs and a significant increase in the chemokine, CXCL10, in bat lung and spleen following infection. In ferrets, there was an increase in the transcription of IFN in the spleen following infection. Liquid chromatography tandem mass spectrometry (LC-MS/MS) on lung tissue from bats and ferrets was performed at 0 and 60 hpe to obtain a global overview of viral and host protein expression. Gene Ontology (GO) enrichment analysis of immune pathways revealed that six pathways, including a number involved in cell mediated immunity were more likely to be upregulated in bat lung compared to ferrets. GO analysis also revealed enrichment of the type I IFN signaling pathway in bats and ferrets. This study contributes important comparative data on differences in the dissemination of HeV and the first to provide comparative data on the activation of immune pathways in bats and ferrets in vivo following infection.

中文翻译：

亨德拉病毒对蝙蝠和雪貂的急性实验感染：洞悉水库宿主和易感模型物种的早期宿主反应。

蝙蝠是许多人畜共患病毒的天然宿主，其中包括在人和其他易感宿主中引起严重临床疾病的亨德拉病毒（HeV）。我们对蝙蝠避免被HeV等病毒感染后避免临床疾病的能力的了解主要来自于针对先天免疫的体外研究。缺乏关于宿主体内对感染的早期反应的信息，与蝙蝠与受疾病折磨的动物相比，没有蝙蝠反应的比较数据。在这项研究中，我们检查了暴露（hpe）后12、36和60小时的HeV复制位点和感染的澳大利亚黑蝇狐和雪貂的免疫反应。蝙蝠在60 hpe时检测到病毒抗原，并将其限制在肺中，而在雪貂中，有证据表明60 hpe会传播广泛的病毒RNA和抗原。IFN的mRNA表达揭示了I型和III型IFN的拮抗作用，感染后蝙蝠肺和脾脏中的趋化因子CXCL10显着增加。在雪貂中，感染后脾脏中IFN的转录增加。在0和60 hpe对来自蝙蝠和雪貂的肺组织进行液相色谱串联质谱分析（LC-MS / MS），以全面了解病毒和宿主蛋白的表达。免疫途径的基因本体论（GO）富集分析显示，与雪貂相比，蝙蝠肺中的6种途径（包括许多参与细胞介导的免疫的途径）更可能被上调。GO分析还揭示了蝙蝠和雪貂中I型IFN信号通路的富集。这项研究提供了有关HeV传播差异的重要比较数据，并且首次提供了有关感染后体内蝙蝠和雪貂体内免疫途径激活的比较数据。

更新日期：2020-03-30

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11