Transcriptome Profiling of the Virus-Induced Innate Immune Response in Pteropus vampyrus and Its Attenuation by Nipah Virus Interferon Antagonist Functions
Transcriptome Profiling of the Virus-Induced Innate Immune Response in Pteropus vampyrus and Its Attenuation by Nipah Virus Interferon Antagonist Functions
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DOI：
10.1128/jvi.00302-15
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发表时间：
2015-08-01
影响因子：
5.4
通讯作者：
Shaw, Megan L.
中科院分区：
文献类型：
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作者：
Glennon, Nicole B.;Jabado, Omar;Shaw, Megan L.
蝙蝠是几种病毒的重要宿主，其中许多病毒在人类中引起致命感染，但在蝙蝠中的致病性降低。由于先天免疫反应对控制病毒至关重要，因此蝙蝠的这种反应的性质及其与其他哺乳动物的不同之处引起了极大的兴趣。利用下一代转录组测序（mRNA-seq），我们分析了狐蝠肾（PVK）细胞对新城疫病毒（NDV）的转录反应，NDV是一种已知在哺乳动物细胞中引发强烈先天免疫反应的禽副粘病毒。已知翼猴属是尼帕病毒和亨德拉病毒的宿主。对200 - 300个受调控基因的分析显示，干扰素（IFN）和抗病毒途径的基因在ndv感染的PVK细胞中高度上调，包括β IFN、RIG-I、MDA5、ISG15和IRF1基因。ndv感染的细胞还上调了一些先前未被表征为抗病毒的基因，如RND1、SERTAD1、CHAC1和MORC3。事实上，我们发现在PVK细胞中，IFN和NDV感染都能诱导MORC3，但在人类A549细胞中，这两种刺激都不能诱导MORC3。与NDV感染相比，HeV和NiV感染PVK细胞不能诱导这些先天免疫应答基因。同样，在PVK细胞感染表达NiV IFN拮抗剂蛋白V和w的重组ndv后，观察到反应减弱。这项研究首次提供了蝙蝠病毒诱导的强效先天免疫反应的全球图谱，并表明亨尼帕病毒IFN拮抗剂机制可能在蝙蝠细胞中活跃。蝙蝠是许多高致病性人类病毒的宿主，包括亨尼帕病毒、溶血病毒、严重急性呼吸综合征冠状病毒和丝状病毒，许多其他病毒也已从蝙蝠中分离出来。据报道，病毒感染在蝙蝠种群中无症状或严重减弱。尽管它们对病毒维持具有重要的生态意义，但对它们的免疫系统和病毒控制机制的研究直到最近才开始。尼帕病毒和亨德拉病毒是与人类高死亡率相关的两种副粘病毒，其宿主是狐蝠属蝙蝠。对吸血假单胞虫蝙蝠对病毒感染的先天免疫反应有了更深入的了解，可能会解释蝙蝠是如何成为如此多病毒的宿主的。
Bats are important reservoirs for several viruses, many of which cause lethal infections in humans but have reduced pathogenicity in bats. As the innate immune response is critical for controlling viruses, the nature of this response in bats and how it may differ from that in other mammals are of great interest. Using next-generation transcriptome sequencing (mRNA-seq), we profiled the transcriptional response of Pteropus vampyrus bat kidney (PVK) cells to Newcastle disease virus (NDV), an avian paramyxovirus known to elicit a strong innate immune response in mammalian cells. The Pteropus genus is a known reservoir of Nipah virus (NiV) and Hendra virus (HeV). Analysis of the 200 to 300 regulated genes showed that genes for interferon (IFN) and antiviral pathways are highly upregulated in NDV-infected PVK cells, including genes for beta IFN, RIG-I, MDA5, ISG15, and IRF1. NDV-infected cells also upregulated several genes not previously characterized to be antiviral, such as RND1, SERTAD1, CHAC1, and MORC3. In fact, we show that MORC3 is induced by both IFN and NDV infection in PVK cells but is not induced by either stimulus in human A549 cells. In contrast to NDV infection, HeV and NiV infection of PVK cells failed to induce these innate immune response genes. Likewise, an attenuated response was observed in PVK cells infected with recombinant NDVs expressing the NiV IFN antagonist proteins V and W. This study provides the first global profile of a robust virus-induced innate immune response in bats and indicates that henipavirus IFN antagonist mechanisms are likely active in bat cells.IMPORTANCEBats are the reservoir host for many highly pathogenic human viruses, including henipaviruses, lyssaviruses, severe acute respiratory syndrome coronavirus, and filoviruses, and many other viruses have also been isolated from bats. Viral infections are reportedly asymptomatic or heavily attenuated in bat populations. Despite their ecological importance to viral maintenance, research into their immune system and mechanisms for viral control has only recently begun. Nipah virus and Hendra virus are two paramyxoviruses associated with high mortality rates in humans and whose reservoir is the Pteropus genus of bats. Greater knowledge of the innate immune response of P. vampyrus bats to viral infection may elucidate how bats serve as a reservoir for so many viruses.