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Marburg and Ebola virus infections elicit a complex, muted inflammatory state in bats
bioRxiv - Microbiology Pub Date : 2021-12-08 , DOI: 10.1101/2020.04.13.039503
Anitha D. Jayaprakash , Adam J. Ronk , Abhishek N. Prasad , Michael F. Covington , Kathryn R. Stein , Toni M. Schwarz , Saboor Hekmaty , Karla A. Fenton , Thomas W. Geisbert , Christopher F. Basler , Alexander Bukreyev , Ravi Sachidanandam

The Marburg and Ebola filoviruses cause a severe, often fatal, disease in humans and nonhuman primates but have only subclinical effects in bats, including Egyptian rousettes, which are a natural reservoir of Marburg virus. A fundamental question is why these viruses are highly pathogenic in humans but fail to cause disease in bats. To understand how bats resist the disease caused by filoviruses, we infected one cohort of Egyptian rousette bats with Marburg virus and another cohort with Ebola virus and harvested multiple tissues for mRNA expression analysis. While virus transcripts were found primarily in the liver, Principal component analysis (PCA) revealed coordinated changes across multiple tissues. Gene signatures in kidney and liver pointed at induction of vasodilation, reduction of coagulation and changes in the regulation of iron metabolism. Signatures of immune response detected in spleen and liver indicated a robust anti-inflammatory state signified by macrophages in the M2 state and an active T cell response. Many of the responsive genes were found to be evolutionarily divergent, providing a framework for understanding the differences in outcomes of filovirus infections between bats and humans. In this study, we outline multiple interconnected pathways that respond to infection by MARV and EBOV, providing insights into the complexity of the mechanisms that enable bats to resist the disease caused by filoviral infections. The results have the potential to aid in the development of new strategies to effectively mitigate and treat the disease caused by these viruses in humans.

中文翻译:

马尔堡病毒和埃博拉病毒感染引起蝙蝠复杂的、无声的炎症状态

马尔堡病毒和埃博拉病毒丝状病毒在人类和非人类灵长类动物中引起严重的、通常是致命的疾病,但对蝙蝠只有亚临床影响,包括埃及红斑蚊,它们是马尔堡病毒的天然宿主。一个基本问题是,为什么这些病毒对人类具有高致病性,但不会在蝙蝠中引起疾病​​。为了了解蝙蝠如何抵抗由丝状病毒引起的疾病,我们用马尔堡病毒感染了一组埃及罗赛特蝙蝠,用埃博拉病毒感染了另一组,并采集了多个组织进行 mRNA 表达分析。虽然病毒转录物主要在肝脏中发现,但主成分分析 (PCA) 揭示了跨多个组织的协调变化。肾脏和肝脏中的基因特征指向血管舒张的诱导,凝血的减少和铁代谢调节的变化。在脾脏和肝脏中检测到的免疫反应特征表明处于 M2 状态的巨噬细胞和活跃的 T 细胞反应所代表的强大的抗炎状态。发现许多响应基因在进化上是不同的,这为理解蝙蝠和人类之间的丝状病毒感染结果的差异提供了一个框架。在这项研究中,我们概述了对 MARV 和 EBOV 感染做出反应的多个相互关联的途径,从而深入了解使蝙蝠能够抵抗由丝状病毒感染引起的疾病的机制的复杂性。结果有可能有助于开发新策略,以有效减轻和治疗由这些病毒引起的人类疾病。在脾脏和肝脏中检测到的免疫反应特征表明处于 M2 状态的巨噬细胞和活跃的 T 细胞反应所代表的强大的抗炎状态。发现许多响应基因在进化上是不同的,这为理解蝙蝠和人类之间的丝状病毒感染结果的差异提供了一个框架。在这项研究中,我们概述了对 MARV 和 EBOV 感染做出反应的多个相互关联的途径,从而深入了解使蝙蝠能够抵抗由丝状病毒感染引起的疾病的机制的复杂性。结果有可能有助于开发新策略,以有效减轻和治疗由这些病毒引起的人类疾病。在脾脏和肝脏中检测到的免疫反应特征表明处于 M2 状态的巨噬细胞和活跃的 T 细胞反应所代表的强大的抗炎状态。发现许多响应基因在进化上是不同的,这为理解蝙蝠和人类之间的丝状病毒感染结果的差异提供了一个框架。在这项研究中,我们概述了对 MARV 和 EBOV 感染做出反应的多个相互关联的途径,从而深入了解使蝙蝠能够抵抗由丝状病毒感染引起的疾病的机制的复杂性。结果有可能有助于开发新策略,以有效减轻和治疗由这些病毒引起的人类疾病。
更新日期:2021-12-11
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