Inhibitory role of the host apoptogenic gene PKR in the establishment of persistent infection by encephalomyocarditis virus in U937 cells.
Inhibitory role of the host apoptogenic gene PKR in the establishment of persistent infection by encephalomyocarditis virus in U937 cells.
复制标题
宿主凋亡基因PKR对U937细胞脑心肌炎病毒持续感染建立的抑制作用。
DOI：
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发表时间：
1999
影响因子：
11.1
通讯作者：
A. Lau
中科院分区：
文献类型：
--
作者：
M. C. Yeung;D. L. Chang;Randell E. Camantigue;A. Lau
HIV-1和B型肝炎病毒等病毒的持续感染可对健康造成长期危害。由于持续性感染的建立涉及宿主和病毒的密切相互作用和调整，因此建立一种范式将是有益的，通过该范式，正常的溶细胞病毒感染可以容易地转化为持续性感染，从而可以检查发展持续性感染的不同阶段。本文描述了这样一个模型系统。高溶细胞性脑心肌炎病毒（EMCV）感染转化为持续感染的结果，抑制表达的双链RNA依赖的蛋白激酶（PKR）在前单核细胞U937细胞。由于PKR的致瘤潜力，PKR的缺乏导致EMCV感染的U937细胞中病毒诱导的凋亡延迟，从而最终在这些细胞中建立持续的EMCV感染（U9 K-AV 2）。这是一种真正的持续性感染，通过感染细胞作为长期病毒脱落培养物繁殖的能力来证明;电子显微镜研究显示存在细胞内EMCV病毒体和染色质凝聚;检测到病毒诱导的染色体DNA片段化和致突变性p53和IL-1 β转化酶的持续表达;以及通过逆转录-PCR证明EMCV转录活跃。此外，随着时间的推移，在U9 K-AV 2培养物中观察到宿主-病毒共进化：U9 K-AV 2细胞表现出较慢的生长速率，对病毒超感染的抗性，以及IFN-α合成的停止，而EMCV的感染性急剧减弱。最后，该模型的适用性研究建立持续感染的其他病毒，如仙台病毒和呼肠孤病毒的数据。
Persistent infections by viruses such as HIV-1 and hepatitis B virus can pose long-term health hazards. Because establishment of persistent infections involves close interactions and adjustments in both host and virus, it would be informative to establish a paradigm with which a normally cytolytic viral infection can be easily converted to persistent infection, so that the different stages in developing persistent infection can be examined. Such a model system is described in this paper. Highly cytolytic encephalomyocarditis virus (EMCV) infection was shifted to persistent infection as a result of repressed expression of the double-stranded RNA-dependent protein kinase (PKR) in the promonocytic U937 cells. Because of the apoptogenic potential of PKR, a deficiency of PKR resulted in a delay in virus-induced apoptosis in EMCV-infected U937 cells, allowing the eventual establishment of persistent EMCV infection in these cells (U9K-AV2). That this was a bona fide persistent infection was demonstrated by the ability of infected cells to propagate as long-term virus-shedding cultures; electron microscopy studies showing presence of intracellular EMCV virions and chromatin condensation; detection of virus-induced chromosomal DNA fragmentation and sustained expression of apoptogenic p53 and IL-1beta converting enzyme; and demonstration of active EMCV transcription by reverse transcription-PCR. In addition, a host-virus coevolution was observed in U9K-AV2 cultures over time: U9K-AV2 cells exhibited slower growth rates, resistance to viral super-infection, and cessation of IFN-alpha synthesis, whereas the infectivity of EMCV was drastically attenuated. Finally, data are presented on the suitability of this model to study establishment of persistent infection by other viruses such as Sendai virus and reovirus.
影响因子：
--
作者：
G. Pfeifer;A. Riggs
通讯作者：
G. Pfeifer;A. Riggs
DOI：
10.1073/pnas.91.14.6288
发表时间：
1994-07-05
影响因子：
11.1
作者：
KUMAR, A;HAQUE, J;WILLIAMS, BRG
通讯作者：
WILLIAMS, BRG