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血脑脊髓液屏障作为严重急性呼吸综合征冠状病毒2(SARS-CoV-2)病毒的潜在进入位点

The Blood-Cerebrospinal Fluid Barrier as a Potential Entry Site for the SARS-CoV-2 Virus.

作者信息

Solár Peter, Šerý Omar, Vojtíšek Tomáš, Krajsa Jan, Srník Michal, Dziedzinská Radka, Králík Petr, Kessler Markéta, Dubový Petr, Joukal Andrea, Balcar Vladimir J, Joukal Marek

机构信息

Department of Anatomy, Faculty of Medicine, Masaryk University, Brno, Czech Republic.

Department of Forensic Medicine, St. Anne's Faculty Hospital, Brno, Czech Republic.

出版信息

J Med Virol. 2025 Jan;97(1):e70184. doi: 10.1002/jmv.70184.

DOI:10.1002/jmv.70184
PMID:39835622
Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an RNA virus responsible for coronavirus disease 2019 (COVID-19). While SARS-CoV-2 primarily targets the lungs and airways, it can also infect other organs, including the central nervous system (CNS). The aim of this study was to investigate whether the choroid plexus could serve as a potential entry site for SARS-CoV-2 into the brain. Tissue samples from 24 deceased COVID-19-positive individuals were analyzed. Reverse transcription real-time PCR (RT-qPCR) was performed on selected brain regions, including the choroid plexus, to detect SARS-CoV-2 viral RNA. Additionally, immunofluorescence staining and confocal microscopy were used to detect and localize two characteristic proteins of SARS-CoV-2: the spike protein S1 and the nucleocapsid protein. RT-qPCR analysis confirmed the presence of SARS-CoV-2 viral RNA in the choroid plexus. Immunohistochemical staining revealed viral particles localized in the epithelial cells of the choroid plexus, with the spike protein S1 detected in the late endosomes. Our findings suggest that the blood-cerebrospinal fluid (B-CSF) barrier in the choroid plexus serves as a route of entry for SARS-CoV-2 into the CNS. This study contributes to the understanding of the mechanisms underlying CNS involvement in COVID-19 and highlights the importance of further research to explore potential therapeutic strategies targeting this entry pathway.

摘要

严重急性呼吸综合征冠状病毒2(SARS-CoV-2)是一种导致2019冠状病毒病(COVID-19)的RNA病毒。虽然SARS-CoV-2主要靶向肺部和气道,但它也能感染包括中枢神经系统(CNS)在内的其他器官。本研究的目的是调查脉络丛是否可能作为SARS-CoV-2进入大脑的潜在入口部位。对24名COVID-19阳性死亡个体的组织样本进行了分析。对包括脉络丛在内的选定脑区进行逆转录实时PCR(RT-qPCR),以检测SARS-CoV-2病毒RNA。此外,免疫荧光染色和共聚焦显微镜用于检测和定位SARS-CoV-2的两种特征性蛋白:刺突蛋白S1和核衣壳蛋白。RT-qPCR分析证实脉络丛中存在SARS-CoV-2病毒RNA。免疫组织化学染色显示病毒颗粒定位于脉络丛上皮细胞中,在晚期内体中检测到刺突蛋白S1。我们的研究结果表明,脉络丛中的血脑脊液(B-CSF)屏障是SARS-CoV-2进入中枢神经系统的一条途径。本研究有助于理解中枢神经系统参与COVID-19的潜在机制,并强调进一步研究探索针对这一进入途径的潜在治疗策略的重要性。

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