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人成纤维样滑膜细胞感染基孔肯雅病毒的蛋白质组学分析:鉴定与基孔肯雅病毒复制和细胞发病机制相关的宿主因子。

Proteomic analysis of CHIKV-infected human fibroblast-like synoviocytes: Identification of host factors potentially associated with CHIKV replication and cellular pathogenesis.

机构信息

Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand.

Proteomics Research Laboratory, Genome Institute, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani, Thailand.

出版信息

Microbiol Immunol. 2020 Jun;64(6):445-457. doi: 10.1111/1348-0421.12793. Epub 2020 May 12.

Abstract

Chikungunya virus (CHIKV) is a mosquito-borne virus that causes arthralgic fever. Fibroblast-like synoviocytes play a key role in joint damage in inflammatory arthritides and can additionally serve as target cells for CHIKV infection. To gain a better understanding of CHIKV-induced arthralgia, the interaction between CHIKV and synoviocytes was investigated at the protein level. A gel-enhanced liquid chromatography-mass spectrometry (GeLC-MS/MS) approach was used to examine protein expression from primary human fibroblast-like synoviocytes (HFLS) infected with clinical isolates of CHIKV at 12 and 24 hr post infection. Our analysis identified 259 and 241 proteins of known function that were differentially expressed (>1.5 or <-1.5 fold change) following CHIKV infection at 12 and 24 hpi, respectively. These proteins are involved in cellular homeostasis, including cellular trafficking, cytoskeletal organization, immune response, metabolic process, and protein modification. Some of these proteins have previously been reported to participate in arthralgia/arthritis and the death of infected cells. Our results provide information on the CHIKV-induced modulation of cellular proteins of HFLS at an early stage of infection, as well as highlighting biological processes associated with CHIKV infection in the main target cells of the joint.

摘要

基孔肯雅热病毒(CHIKV)是一种虫媒病毒,可引起关节痛性发热。成纤维样滑膜细胞在炎症性关节炎的关节损伤中起着关键作用,并且可以作为 CHIKV 感染的靶细胞。为了更好地了解 CHIKV 引起的关节痛,在蛋白质水平上研究了 CHIKV 与滑膜细胞之间的相互作用。采用凝胶增强液相色谱-质谱联用(GeLC-MS/MS)方法检测感染临床分离的 CHIKV 12 和 24 小时后的原代人成纤维样滑膜细胞(HFLS)中的蛋白质表达。我们的分析鉴定了 259 种和 241 种已知功能的蛋白质,它们在 CHIKV 感染后 12 和 24 hpi 时的表达水平差异(>1.5 或<-1.5 倍变化)。这些蛋白质参与细胞内稳态,包括细胞内运输、细胞骨架组织、免疫反应、代谢过程和蛋白质修饰。其中一些蛋白质以前曾被报道参与关节痛/关节炎和感染细胞的死亡。我们的结果提供了在感染早期 HFLS 细胞中 CHIKV 诱导的细胞蛋白调节的信息,并强调了与关节中主要靶细胞的 CHIKV 感染相关的生物学过程。

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