Abstract：
Background: Chikungunya is a zoonotic disease caused by the Chikungunya virus (CHIKV), primarily transmitted to humans through infected Aedes mosquitoes. The infection is characterized by symptoms such as high fever, musculoskeletal pain, polyarthritis, and a rash, which can lead to severe complications such as encephalitis, meningitis, and even fatalities. While many disease manifestations resemble those of other viral infections, chronic arthritis caused by CHIKV is unique, and its molecular mechanisms remain ill-defined. Materials and Methods: Proteomics data from both cellular and patient levels of CHIKV infection were curated from PubMed and screened using inclusion and exclusion criteria. Patient serum proteomics data obtained from P RIDE underwent reanalysis using Proteome Discoverer 2.2. Enrichment and protein-protein interaction network analysis were conducted on differentially expressed proteins from both serum and cellular datasets. Metabolite data from CHIKV-infected patients were further retrieved, and their protein binding partners were identified using BindingDB. The protein-metabolite interaction pathway was further developed using MetaboAnalyst. Results: The proteomics data analysis revealed differential expression of proteins involved in critical host mechanisms, such as cholesterol metabolism and mRNA splicing, during CHIKV infection. Consistent upregulation of two actin cytoskeleton proteins, TAGLN2 and PFN1, was noted in both serum and cellular datasets, and their upregulations are associated with arthritis. Furthermore, alterations in purine metabolism were observed in the integrative proteome-metabolome analysis, correlating with cytoskeletal remodelling. Conclusion: Collectively, this integrative view sheds light on the involvement of actin cytoskeleton remodeling proteins and purine metabolic pathways in the development of arthritis during CHIKV infection.
摘要：
背景：基孔肯雅病是由基孔肯雅病毒（CHIKV）引起的人畜共患疾病，主要通过受感染的伊蚊传播给人类。感染的特征是高烧等症状，肌肉骨骼疼痛，多发性关节炎,还有皮疹,这可能导致严重的并发症，如脑炎，脑膜炎,甚至死亡。虽然许多疾病表现类似于其他病毒感染，CHIKV引起的慢性关节炎是独一无二的，其分子机制仍不明确。材料和方法：从PubMed收集来自CHIKV感染的细胞和患者水平的蛋白质组学数据，并使用纳入和排除标准进行筛选。使用蛋白质组发现者2.2对从PRIDE获得的患者血清蛋白质组学数据进行了重新分析。对来自血清和细胞数据集的差异表达的蛋白质进行富集和蛋白质-蛋白质相互作用网络分析。进一步检索了CHIKV感染患者的代谢物数据，并使用BindingDB鉴定了它们的蛋白质结合伴侣。使用MetaboAnalyst进一步开发了蛋白质-代谢物相互作用途径。结果：蛋白质组学数据分析揭示了参与关键宿主机制的蛋白质的差异表达，如胆固醇代谢和mRNA剪接，在CHIKV感染期间。两种肌动蛋白细胞骨架蛋白的一致上调，TAGLN2和PFN1在血清和细胞数据集中都有记录，他们的上调与关节炎有关。此外，在综合蛋白质组-代谢组分析中观察到嘌呤代谢的改变，与细胞骨架重塑相关。结论：集体，这一综合观点揭示了肌动蛋白细胞骨架重塑蛋白和嘌呤代谢途径参与CHIKV感染期间关节炎的发展。
