Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
Key Laboratory of Zoonosis of Ministry of Agriculture and Rural Affairs, South China Agricultural University, Guangzhou, Guangdong, China.
Front Cell Infect Microbiol. 2023 Sep 25;13:1267629. doi: 10.3389/fcimb.2023.1267629. eCollection 2023.
The masked palm civet () serves as a reservoir in transmitting pathogens, such as , to humans. However, the pathogenesis of infection in masked palm civets has not been explored. We studied the molecular changes in the brain tissue of masked palm civets chronically infected with ME49.
The differentially expressed proteins in the brain tissue were investigated using iTRAQ and bioinformatics.
A total of 268 differential proteins were identified, of which 111 were upregulated and 157 were downregulated. KEGG analysis identified pathways including PI3K-Akt signaling pathway, proteoglycans in cancer, carbon metabolism, T-cell receptor signaling pathway. Combing transcriptomic and proteomics data, we identified 24 genes that were differentially expressed on both mRNA and protein levels. The top four upregulated proteins were REEP3, REEP4, TEP1, and EEPD1, which was confirmed by western blot and immunohistochemistry. KEGG analysis of these 24 genes identified signaling cascades that were associated with small cell lung cancer, breast cancer, Toll-like receptor signaling pathway, Wnt signaling pathways among others. To understand the mechanism of the observed alteration, we conducted immune infiltration analysis using TIMER databases which identified immune cells that are associated with the upregulation of these proteins. Protein network analysis identified 44 proteins that were in close relation to all four proteins. These proteins were significantly enriched in immunoregulation and cancer pathways including PI3K-Akt signaling pathway, Notch signaling pathway, chemokine signaling pathway, cell cycle, breast cancer, and prostate cancer. Bioinformatics utilizing two cancer databases (TCGA and GEPIA) revealed that the four genes were upregulated in many cancer types including glioblastoma (GBM). In addition, higher expression of REEP3 and EEPD1 was associated with better prognosis, while higher expression of REEP4 and TEP1 was associated with poor prognosis in GBM patients.
We identified the differentially expressed genes in the brain of infected masked palm civets. These genes were associated with various cellular signaling pathways including those that are immune- and cancer-related.
带帽叶猴（）是一种传播病原体的宿主，例如，可以将病原体传播给人类。然而，带帽叶猴感染的发病机制尚未得到探索。我们研究了慢性感染的带帽叶猴脑组织中 ME49 的分子变化。
使用 iTRAQ 和生物信息学研究脑组织中的差异表达蛋白。
共鉴定出 268 个差异蛋白，其中 111 个上调，157 个下调。KEGG 分析鉴定出包括 PI3K-Akt 信号通路、癌症中的蛋白聚糖、碳代谢、T 细胞受体信号通路在内的途径。结合转录组和蛋白质组学数据，我们鉴定出 24 个在 mRNA 和蛋白质水平上均差异表达的基因。上调最明显的四个蛋白是 REEP3、REEP4、TEP1 和 EEPD1，通过 Western blot 和免疫组织化学进一步验证。对这 24 个基因的 KEGG 分析确定了与小细胞肺癌、乳腺癌、Toll 样受体信号通路、Wnt 信号通路等相关的信号级联。为了了解观察到的变化的机制，我们使用 TIMER 数据库进行免疫浸润分析，该分析确定了与这些蛋白上调相关的免疫细胞。蛋白质网络分析确定了与所有四个蛋白密切相关的 44 个蛋白。这些蛋白在免疫调节和癌症途径中显著富集，包括 PI3K-Akt 信号通路、Notch 信号通路、趋化因子信号通路、细胞周期、乳腺癌和前列腺癌。利用两个癌症数据库（TCGA 和 GEPIA）进行的生物信息学分析表明，这四个基因在包括胶质母细胞瘤（GBM）在内的许多癌症类型中均上调。此外，REEP3 和 EEPD1 的高表达与 GBM 患者的较好预后相关，而 REEP4 和 TEP1 的高表达与 GBM 患者的预后不良相关。
我们鉴定了感染的带帽叶猴脑组织中的差异表达基因。这些基因与包括免疫和癌症相关的各种细胞信号通路有关。
