Proteomics informed by transcriptomics reveals Hendra virus sensitizes bat cells to TRAIL-mediated apoptosis
Proteomics informed by transcriptomics reveals Hendra virus sensitizes bat cells to TRAIL-mediated apoptosis
复制标题
DOI：
10.1186/s13059-014-0532-x
复制
发表时间：
2014-01-01
期刊：
影响因子：
12.3
通讯作者：
Wang, Lin-Fa
中科院分区：
文献类型：
--
作者：
Wynne, James W.;Shiell, Brian J.;Wang, Lin-Fa
背景：蝙蝠是新出现的传染性病毒的主要宿主。这些病毒中的许多对人类具有高致病性，但蝙蝠仍然没有症状。蝙蝠控制病毒复制的机制尚不清楚。在这里，我们利用蛋白质组学的整合方法通知转录比较永生化蝙蝠和人类细胞感染后的反应与高致病性蝙蝠传播的亨德拉病毒（HeV.Results）：宿主细胞系之间的反应是显着不同的mRNA和蛋白质水平。人类细胞在感染后8小时表现出最小的反应，随后是mRNA和蛋白质丰度的整体抑制。蝙蝠细胞在感染后8小时表现出强烈的免疫应答，这导致通过肿瘤坏死因子相关凋亡诱导配体（TRAIL）介导的凋亡途径的上调。HeV通过上调死亡受体转录物使蝙蝠细胞对TRAIL介导的凋亡敏感。在48和72小时后infection.Conclusions，蝙蝠细胞表现出显着增加的凋亡细胞death.Conclusions：这是第一次研究全面比较蝙蝠和人类细胞的反应，高致病性人畜共患病病毒。先天性免疫过程的早期诱导，随后是病毒感染的蝙蝠细胞的凋亡，突出了宿主反应中程序性细胞死亡的可能参与。我们的研究首次显示了对来自人类和天然蝙蝠宿主的细胞系中危险的人畜共患病病毒的并行高通量分析。这使得在分子水平上寻找可能影响宿主发病机制的不同机制成为可能。
Background: Bats are a major reservoir of emerging infectious viruses. Many of these viruses are highly pathogenic to humans however bats remain asymptomatic. The mechanism by which bats control viral replication is unknown. Here we utilize an integrated approach of proteomics informed by transcriptomics to compare the response of immortalized bat and human cells following infection with the highly pathogenic bat-borne Hendra virus (HeV).Results: The host response between the cell lines was significantly different at both the mRNA and protein levels. Human cells demonstrated minimal response eight hours post infection, followed by a global suppression of mRNA and protein abundance. Bat cells demonstrated a robust immune response eight hours post infection, which led to the up-regulation of apoptosis pathways, mediated through the tumor necrosis factor-related apoptosis inducing ligand (TRAIL). HeV sensitized bat cells to TRAIL-mediated apoptosis, by up-regulating death receptor transcripts. At 48 and 72 hours post infection, bat cells demonstrated a significant increase in apoptotic cell death.Conclusions: This is the first study to comprehensively compare the response of bat and human cells to a highly pathogenic zoonotic virus. An early induction of innate immune processes followed by apoptosis of virally infected bat cells highlights the possible involvement of programmed cell death in the host response. Our study shows for the first time a side-by-side high-throughput analysis of a dangerous zoonotic virus in cell lines derived from humans and the natural bat host. This enables a way to search for divergent mechanisms at a molecular level that may influence host pathogenesis.