Kuzmin Ivan V, Schwarz Toni M, Ilinykh Philipp A, Jordan Ingo, Ksiazek Thomas G, Sachidanandam Ravi, Basler Christopher F, Bukreyev Alexander
Department of Pathology, The University of Texas Medical Branch, Galveston, Texas, USA.
Galveston National Laboratory, The University of Texas Medical Branch, Galveston, Texas, USA.
J Virol. 2017 Mar 29;91(8). doi: 10.1128/JVI.02471-16. Print 2017 Apr 15.
Marburg (MARV) and Ebola (EBOV) viruses are zoonotic pathogens that cause severe hemorrhagic fever in humans. The natural reservoir of MARV is the Egyptian rousette bat (); that of EBOV is unknown but believed to be another bat species. The Egyptian rousette develops subclinical productive infection with MARV but is refractory to EBOV. Interaction of filoviruses with hosts is greatly affected by the viral interferon (IFN)-inhibiting domains (IID). Our study was aimed at characterization of innate immune responses to filoviruses and the role of filovirus IID in bat and human cells. The study demonstrated that EBOV and MARV replicate to similar levels in all tested cell lines, indicating that permissiveness for EBOV at cell and organism levels do not necessarily correlate. Filoviruses, particularly MARV, induced a potent innate immune response in rousette cells, which was generally stronger than that in human cells. Both EBOV VP35 and VP24 IID were found to suppress the innate immune response in rousette cells, but only VP35 IID appeared to promote virus replication. Along with IFN-α and IFN-β, IFN-γ was demonstrated to control filovirus infection in bat cells but not in human cells, suggesting host species specificity of the antiviral effect. The antiviral effects of bat IFNs appeared not to correlate with induction of IFN-stimulated genes 54 and 56, which were detected in human cells ectopically expressing bat IFN-α and IFN-β. As bat IFN-γ induced the type I IFN pathway, its antiviral effect is likely to be partially induced via cross talk. Bats serve as reservoirs for multiple emerging viruses, including filoviruses, henipaviruses, lyssaviruses, and zoonotic coronaviruses. Although there is no evidence for symptomatic disease caused by either Marburg or Ebola viruses in bats, spillover of these viruses into human populations causes deadly outbreaks. The reason for the lack of symptomatic disease in bats infected with filoviruses remains unknown. The outcome of a virus-host interaction depends on the ability of the host immune system to suppress viral replication and the ability of a virus to counteract the host defenses. Our study is a comparative analysis of the host innate immune response to either MARV or EBOV infection in bat and human cells and the role of viral interferon-inhibiting domains in the host innate immune responses. The data are useful for understanding the interactions of filoviruses with natural and accidental hosts and for identification of factors that influence filovirus evolution.
马尔堡病毒（MARV）和埃博拉病毒（EBOV）是能引起人类严重出血热的人畜共患病原体。马尔堡病毒的天然宿主是埃及果蝠；埃博拉病毒的天然宿主未知，但据信是另一种蝙蝠。埃及果蝠会发生马尔堡病毒的亚临床感染，但对埃博拉病毒具有抗性。丝状病毒与宿主的相互作用受到病毒干扰素（IFN）抑制域（IID）的极大影响。我们的研究旨在表征对丝状病毒的先天免疫反应以及丝状病毒IID在蝙蝠和人类细胞中的作用。该研究表明，埃博拉病毒和马尔堡病毒在所有测试细胞系中的复制水平相似，这表明在细胞和生物体水平上对埃博拉病毒的易感性不一定相关。丝状病毒，特别是马尔堡病毒，在果蝠细胞中诱导了强烈的先天免疫反应，这种反应通常比在人类细胞中更强。发现埃博拉病毒的VP35和VP24 IID均能抑制果蝠细胞中的先天免疫反应，但只有VP35 IID似乎能促进病毒复制。与IFN-α和IFN-β一起，IFN-γ被证明能控制蝙蝠细胞中的丝状病毒感染，但不能控制人类细胞中的感染，这表明抗病毒作用具有宿主物种特异性。蝙蝠IFN的抗病毒作用似乎与IFN刺激基因54和56的诱导无关，这些基因在异位表达蝙蝠IFN-α和IFN-β的人类细胞中被检测到。由于蝙蝠IFN-γ诱导了I型IFN途径，其抗病毒作用可能部分是通过串扰诱导的。蝙蝠是多种新兴病毒的宿主，包括丝状病毒、亨尼帕病毒、狂犬病病毒和人畜共患冠状病毒。尽管没有证据表明蝙蝠感染马尔堡病毒或埃博拉病毒会引发症状性疾病，但这些病毒传播到人类群体中会导致致命疫情爆发。感染丝状病毒的蝙蝠没有症状性疾病的原因仍然未知。病毒与宿主相互作用的结果取决于宿主免疫系统抑制病毒复制的能力以及病毒对抗宿主防御的能力。我们的研究是对蝙蝠和人类细胞中马尔堡病毒或埃博拉病毒感染的宿主先天免疫反应以及病毒干扰素抑制域在宿主先天免疫反应中的作用的比较分析。这些数据有助于理解丝状病毒与天然宿主和意外宿主的相互作用，以及识别影响丝状病毒进化的因素。
