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使用表达纳米荧光素酶的重组基孔肯雅病毒在免疫健全小鼠模型中鉴定软骨细胞为靶细胞

Use of Recombinant Chikungunya Virus expressing Nanoluciferase to Identify Chondrocytes as Target Cells in an Immunocompetent Mouse Model.

作者信息

Legros Vincent, Belarbi Essia, Jeannin Patricia, Geolier Virginie, Kümmerer Beate M, Hardy David, Desprès Philippe, Gessain Antoine, Roques Pierre, Ceccaldi Pierre-Emmanuel, Choumet Valérie

机构信息

Unité Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur, Université Paris Cité, UMR CNRS 3569, Paris, France.

Unité Recherche et Expertise Environnement et Risques Infectieux, Institut Pasteur, Université Paris Cité, Paris, France.

出版信息

J Infect Dis. 2025 Aug 14;232(2):e223-e233. doi: 10.1093/infdis/jiaf232.

Abstract

Chikungunya virus (CHIKV) induces predominantly symptomatic infections, marked by fever, myalgia, rash and polyarthralgia that can last for up to 3 years after infection. Understanding the pathophysiology of CHIKV in the joints is challenging due to limited access to biological samples. Using a reporter virus expressing Nanoluciferase in a mouse model allowed us to monitor viral replication in real-time during acute and postacute phases. We showed viral replication in chondrocyte containing tissue in the metatarsi joints and confirmed with ex vivo analyses viral replication in leg bones and articular cartilages with histological evidence of focal erosive lesions and periarticular inflammation. Moreover, human chondrocytes prove susceptible to CHIKV infection, exhibiting viral production and bioluminescence activity. CHIKV induced apoptosis, the up-regulation of markers associated with cartilage remodeling and altered cytokine production. Our study provides insights into the ability of CHIKV to infect articular cartilages, shedding light on the mechanisms of alphaviral arthritis.

摘要

基孔肯雅病毒(CHIKV)主要引起有症状的感染,其特征为发热、肌痛、皮疹和多关节痛,感染后可持续长达3年。由于获取生物样本的机会有限,了解CHIKV在关节中的病理生理学具有挑战性。在小鼠模型中使用表达纳米荧光素酶的报告病毒使我们能够在急性期和急性后期实时监测病毒复制。我们展示了跗关节中含软骨细胞组织中的病毒复制,并通过离体分析证实了腿骨和关节软骨中的病毒复制,同时有局灶性糜烂性病变和关节周围炎症的组织学证据。此外,人类软骨细胞被证明易受CHIKV感染,表现出病毒产生和生物发光活性。CHIKV诱导细胞凋亡、与软骨重塑相关标志物的上调以及细胞因子产生的改变。我们的研究深入了解了CHIKV感染关节软骨的能力,为甲病毒关节炎的机制提供了线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7723/12349949/2dafb49a0d52/jiaf232f1.jpg

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