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BK 多瘤病毒持续感染、基因组重组和激活的细胞培养模型。

A Cell Culture Model of BK Polyomavirus Persistence, Genome Recombination, and Reactivation.

机构信息

Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA.

Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan, USA.

出版信息

mBio. 2021 Oct 26;12(5):e0235621. doi: 10.1128/mBio.02356-21. Epub 2021 Sep 2.

DOI:10.1128/mBio.02356-21
PMID:34473564
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8546605/
Abstract

BK polyomavirus (BKPyV) is a small nonenveloped DNA virus that establishes a ubiquitous, asymptomatic, and lifelong persistent infection in at least 80% of the world's population. In some immunosuppressed transplant recipients, BKPyV reactivation causes polyomavirus-associated nephropathy and hemorrhagic cystitis. We report a novel model of BKPyV persistence and reactivation using a BKPyV natural host cell line. In this system, viral genome loads remain constant for various times after establishment of persistent infection, during which BKPyV undergoes extensive random genome recombination. Certain recombination events result in viral DNA amplification and protein expression, resulting in production of viruses with enhanced replication ability. BK polyomavirus (BKPyV) generally establishes a persistent subclinical infection in healthy individuals but can cause severe disease in transplant recipients. While an model to study acute replication exists, no practical model with which to study BKPyV persistence is currently available. We established a BKPyV persistence model in cell culture. Our model reveals that the virus can persist for various periods of time before random recombination of the viral genome leads to enhanced replication.

摘要

BK 多瘤病毒(BKPyV)是一种小型无包膜 DNA 病毒,它在全球至少 80%的人口中建立了普遍存在、无症状和终身持续的感染。在一些免疫抑制的移植受者中,BKPyV 再激活导致多瘤病毒相关性肾病和出血性膀胱炎。我们使用 BKPyV 天然宿主细胞系报告了一种新的 BKPyV 持续存在和再激活模型。在该系统中,在持续感染建立后的不同时间,病毒基因组载量保持不变,在此期间,BKPyV 经历广泛的随机基因组重组。某些重组事件导致病毒 DNA 扩增和蛋白表达,从而产生具有增强复制能力的病毒。BK 多瘤病毒(BKPyV)通常在健康个体中建立持续的亚临床感染,但可在移植受者中引起严重疾病。虽然存在研究急性复制的模型,但目前尚无实用的 BKPyV 持续存在模型。我们在细胞培养中建立了 BKPyV 持续存在模型。我们的模型表明,病毒可以持续存在一段时间,然后病毒基因组的随机重组导致复制增强。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8809/8546605/e870cd1c0fb5/mbio.02356-21-f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8809/8546605/becb28f87d90/mbio.02356-21-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8809/8546605/96bd5e6c46ae/mbio.02356-21-f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8809/8546605/128d9ae9f732/mbio.02356-21-f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8809/8546605/dc63711c0092/mbio.02356-21-f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8809/8546605/e870cd1c0fb5/mbio.02356-21-f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8809/8546605/becb28f87d90/mbio.02356-21-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8809/8546605/96bd5e6c46ae/mbio.02356-21-f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8809/8546605/128d9ae9f732/mbio.02356-21-f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8809/8546605/dc63711c0092/mbio.02356-21-f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8809/8546605/e870cd1c0fb5/mbio.02356-21-f005.jpg

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