Temporal Proteomic Analysis of BK Polyomavirus Infection Reveals Virus-Induced G2 Arrest and Highly Effective Evasion of Innate Immune Sensing
Temporal Proteomic Analysis of BK Polyomavirus Infection Reveals Virus-Induced G2 Arrest and Highly Effective Evasion of Innate Immune Sensing
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DOI：
10.1128/jvi.00595-19
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发表时间：
2019-08-01
影响因子：
5.4
通讯作者：
Crump, Colin M.
中科院分区：
文献类型：
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作者：
Caller, Laura G.;Davies, Colin T. R.;Crump, Colin M.
BK多瘤病毒（BKPyV）是一种小的DNA病毒，在大多数人的尿路中建立终身持续性感染。已知BKPyV在肾移植受者中引起严重的发病率，并可导致移植排斥反应。简单的5.2 kbp双链DNA （dsDNA）基因组只表达7种已知的蛋白质；因此，它在很大程度上依赖于宿主机器进行复制。宿主蛋白质组在感染过程中如何变化是理解宿主-病毒相互作用的关键。本研究首次利用定量时间病毒组学技术，对两种人原代上皮细胞中bbb9000宿主蛋白在感染BKPyV 72小时内的整体变化进行了定量分析。这些数据证明了细胞周期进程和伪g(2)阻滞在有效的BKPyV复制中的重要性，以及在整个病毒复制周期中令人惊讶的缺乏先天免疫反应。因此，BKPyV以复杂的方式逃避病原体识别以阻止先天免疫反应的激活。BK多瘤病毒可在免疫抑制患者中引起严重问题，特别是肾移植受者可发展为多瘤病毒相关肾脏疾病。在这项工作中，我们使用先进的蛋白质组学技术来确定在该病毒的整个复制周期中，感染人类尿路两种独立的原代细胞类型（肾脏和膀胱）引起的蛋白质表达变化。我们的发现揭示了由这种病毒引起的一种特定形式的细胞周期阻滞的新细节，重要的是，我们已经确定这种病毒具有逃避宿主细胞防御系统检测的卓越能力。此外，我们的数据为未来肾上皮细胞及其尿路病原体感染的研究提供了重要的资源。
BK polyomavirus (BKPyV) is a small DNA virus that establishes a lifelong persistent infection in the urinary tract of most people. BKPyV is known to cause severe morbidity in renal transplant recipients and can lead to graft rejection. The simple 5.2-kbp double-stranded DNA (dsDNA) genome expresses just seven known proteins; thus, it relies heavily on the host machinery to replicate. How the host proteome changes over the course of infection is key to understanding this host-virus interplay. Here, for the first time quantitative temporal viromics has been used to quantify global changes in >9,000 host proteins in two types of primary human epithelial cells throughout 72 h of BKPyV infection. These data demonstrate the importance of cell cycle progression and pseudo-G(2) arrest in effective BKPyV replication, along with a surprising lack of an innate immune response throughout the whole virus replication cycle. BKPyV thus evades pathogen recognition to prevent activation of innate immune responses in a sophisticated manner.IMPORTANCE BK polyomavirus can cause serious problems in immune-suppressed patients, in particular, kidney transplant recipients who can develop polyomavirus-associated kidney disease. In this work, we have used advanced proteomics techniques to determine the changes to protein expression caused by infection of two independent primary cell types of the human urinary tract (kidney and bladder) throughout the replication cycle of this virus. Our findings have uncovered new details of a specific form of cell cycle arrest caused by this virus, and, importantly, we have identified that this virus has a remarkable ability to evade detection by host cell defense systems. In addition, our data provide an important resource for the future study of kidney epithelial cells and their infection by urinary tract pathogens.