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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Establishment of papillomavirus infection is enhanced by promyelocytic leukemia protein (PML) expression
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Establishment of papillomavirus infection is enhanced by promyelocytic leukemia protein (PML) expression

机译:早幼粒细胞白血病蛋白(PML)表达可增强乳头瘤病毒感染的建立

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Previous studies have suggested that most papillomaviruses enter the host cell via clathrin-dependent receptor-mediated endocytosis but have not addressed later steps in viral entry. To examine these events, we followed the localization of L2 and packaged DNA after entry of infectious virions or L1/L2 pseudovirions. Confocal microscopic analyses of HeLa cells showed a time-dependent uncoating of capsids in cytoplasmic vesicles and the accumulation of both L2 and viral DNA at distinct nuclear domains identified as nuclear domain 10 (ND10). Both L2 and the pseudogenome had a punctate distribution and localized to ND10 in promyelocytic leukemia protein (PML)-expressing cells, whereas L2 had a diffuse nuclear distribution in PML-/- cells. The number of pseudovirus-infected cells was an order of magnitude higher in the PML+ cells compared with the PML-/- cells, and viral genome transcription after infection with authentic bovine papillomavirus virions was similarly elevated in PML+ cells. The results identify a role for PML in the enhancement of viral infectivity in the early part of the life cycle. We propose a model in which L2 chaperones the viral genome to ND10 to efficiently initiate viral transcription.
机译:先前的研究表明,大多数乳头瘤病毒通过网格蛋白依赖性受体介导的内吞作用进入宿主细胞,但并未解决病毒进入的后续步骤。为了检查这些事件,我们跟踪了感染性病毒颗粒或L1 / L2假病毒颗粒进入后L2和包装DNA的定位。 HeLa细胞的共聚焦显微镜分析显示,胞质囊中的衣壳具有随时间变化的脱膜作用,L2和病毒DNA的积累在被识别为核域10(ND10)的不同核域中。 L2和假基因组都具有点状分布,并位于表达早幼粒细胞白血病蛋白(PML)的细胞中,定位于ND10,而L2在PML-/-细胞中具有弥散的核分布。与PML-/-细胞相比,在PML +细胞中伪病毒感染的细胞数量增加了一个数量级,在真牛乳头瘤病毒病毒体感染后,病毒基因组转录在PML +细胞中也同样升高。这些结果确定了PML在生命周期早期提高病毒感染性中的作用。我们提出了一个模型,其中L2伴侣将病毒基因组转移到ND10以有效地启动病毒转录。

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