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细小病毒 B19V 非结构蛋白 NS1 诱导非自身免疫小鼠产生双链脱氧核糖核酸自身抗体和靶器官损伤。

Parvovirus B19V Nonstructural Protein NS1 Induces Double-Stranded Deoxyribonucleic Acid Autoantibodies and End-Organ Damage in Nonautoimmune Mice.

机构信息

Department of Biological and Environmental Science and Nanoscience Center, University of Jyvaskyla, Finland.

Quest Diagnostics Nichols Institute, Immunology R&D, San Juan Capistrano, California.

出版信息

J Infect Dis. 2019 Apr 16;219(9):1418-1429. doi: 10.1093/infdis/jiy614.

DOI:10.1093/infdis/jiy614
PMID:30346568
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6468957/
Abstract

BACKGROUND

Viral infection is implicated in development of autoimmunity. Parvovirus B19 (B19V) nonstructural protein, NS1, a helicase, covalently modifies self double-stranded deoxyribonucleic acid (dsDNA) and induces apoptosis. This study tested whether resulting apoptotic bodies (ApoBods) containing virally modified dsDNA could induce autoimmunity in an animal model.

METHODS

BALB/c mice were inoculated with (1) pristane-induced, (2) B19V NS1-induced, or (3) staurosporine-induced ApoBods. Serum was tested for dsDNA autoantibodies by Crithidia luciliae staining and enzyme-linked immunosorbent assay. Brain, heart, liver, and kidney pathology was examined. Deposition of self-antigens in glomeruli was examined by staining with antibodies to dsDNA, histones H1 and H4, and TATA-binding protein.

RESULTS

The B19V NS1-induced ApoBod inoculation induced dsDNA autoantibodies in a dose-dependent fashion. Histopathological features of immune-mediated organ damage were evident in pristane-induced and NS1-induced ApoBod groups; severity scores were higher in these groups than in staurosporine-treated groups. Tissue damage was dependent on NS1-induced ApoBod dose. Nucleosomal antigens were deposited in target tissue from pristane-induced and NS1-induced ApoBod inoculated groups, but not in the staurosporine-induced ApoBod inoculated group.

CONCLUSIONS

This study demonstrated proof of principle in an animal model that virally modified dsDNA in apoptotic bodies could break tolerance to self dsDNA and induce dsDNA autoantibodies and end-organ damage.

摘要

背景

病毒感染与自身免疫的发展有关。细小病毒 B19（B19V）非结构蛋白 NS1 是一种解旋酶，可使自身双链脱氧核糖核酸（dsDNA）共价修饰，并诱导细胞凋亡。本研究检测了含有病毒修饰 dsDNA 的凋亡小体（ApoBod）是否会在动物模型中诱导自身免疫。

方法

BALB/c 小鼠接种（1）降植烷诱导、（2）B19V NS1 诱导或（3）星形孢菌素诱导的 ApoBod。通过克鲁利西亚假丝酵母染色和酶联免疫吸附试验检测血清 dsDNA 自身抗体。检查脑、心、肝和肾的病理。通过用 dsDNA、组蛋白 H1 和 H4 以及 TATA 结合蛋白的抗体染色，检查肾小球中自身抗原的沉积。

结果

B19V NS1 诱导的 ApoBod 接种以剂量依赖的方式诱导 dsDNA 自身抗体。在降植烷诱导和 NS1 诱导的 ApoBod 组中观察到免疫介导的器官损伤的组织病理学特征；这些组的严重程度评分高于星形孢菌素处理组。组织损伤取决于 NS1 诱导的 ApoBod 剂量。来自降植烷诱导和 NS1 诱导的 ApoBod 接种组的核小体抗原沉积在靶组织中，但星形孢菌素诱导的 ApoBod 接种组没有。

结论

本研究在动物模型中证明了一个原理，即凋亡小体中的病毒修饰 dsDNA 可以破坏对自身 dsDNA 的耐受性，并诱导 dsDNA 自身抗体和终末器官损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97d5/6468957/1e1b8a873343/jiy61405.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97d5/6468957/6786ec582a06/jiy61401.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97d5/6468957/95cd98d74a77/jiy61402.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97d5/6468957/c2218748372f/jiy61403.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97d5/6468957/cfaa3fddb39a/jiy61404.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97d5/6468957/1e1b8a873343/jiy61405.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97d5/6468957/6786ec582a06/jiy61401.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97d5/6468957/95cd98d74a77/jiy61402.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97d5/6468957/c2218748372f/jiy61403.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97d5/6468957/cfaa3fddb39a/jiy61404.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97d5/6468957/1e1b8a873343/jiy61405.jpg

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本文引用的文献

1
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2
Proinflammatory effects of interferon gamma in mouse adenovirus 1 myocarditis.γ干扰素在鼠腺病毒 1 型心肌炎中的促炎作用。
J Virol. 2015 Jan;89(1):468-79. doi: 10.1128/JVI.02077-14. Epub 2014 Oct 15.
3
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肾小球疾病中的自身免疫与感染
Microorganisms. 2023 Sep 2;11(9):2227. doi: 10.3390/microorganisms11092227.
4
The Relationship Between the Global Burden of Influenza From 2017 to 2019 and COVID-19: Descriptive Epidemiological Assessment.2017 年至 2019 年全球流感负担与 COVID-19 之间的关系：描述性流行病学评估。
JMIR Public Health Surveill. 2021 Mar 2;7(3):e24696. doi: 10.2196/24696.
5
Parvovirus B19 infection and kidney injury: report of 4 cases and analysis of immunization and viremia in an adult cohort of 100 patients undergoing a kidney biopsy.细小病毒 B19 感染与肾损伤：4 例报告，并对 100 例行肾活检的成年患者队列中的免疫接种和病毒血症进行分析。
BMC Nephrol. 2020 Jul 9;21(1):260. doi: 10.1186/s12882-020-01911-9.
6
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BMJ Case Rep. 2020 Mar 18;13(3):e233485. doi: 10.1136/bcr-2019-233485.
7
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5
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7
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8
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9
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10
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Toxicol Pathol. 2010 Dec;38(7 Suppl):5S-81S. doi: 10.1177/0192623310386499.