The brain microvascular endothelial cells (ECs) play an important role in protecting the brain from hazardous pathogens. However, some viral pathogens can smartly modulate the endothelial pathways to gain entry inside the brain. Further, these viruses can cause endothelial dysfunction which could develop serious neurological ailments. Epstein-Barr virus (EBV), an oncogenic virus, has also been linked to various neurological disorders. The virus primarily infects epithelial and B cells, however, it also has a tendency to infect ECs and cause endothelial activation. However, the impact of EBV influence on ECs is still underexplored. Studying the early events of virus-mediated cellular modulation could help in understanding the virus' infection strategy or aftermath. Raman microspectroscopy has been widely utilized in biomedical sciences to decipher cellular changes. To understand the EBV-influenced EC modulation by studying intracellular biomolecular changes at early time points, we utilized the Raman microspectroscopy tool. We treated the ECs with EBV and acquired the Raman spectra at different time points (2, 4, 6, 12, 24 and 36 h) and different sites (nucleus and periphery) to check changes in Raman intensities associated with specific biomolecules. In the EBV-treated cells, the status of various biomolecules in terms of Raman intensities was observed to be altered compared with uninfected cells. Specifically, the cholesterol, polysaccharide, nucleotides, nucleic acid and proline moieties were altered at different time points. We also investigated the possible correlation between these molecules using molecular network analysis and observed various associated factors. These factors could be influenced by EBV to alter the associated biomolecular levels. Our study paves the pathway to study EBV infection in human brain microvascular ECs and highlights specific biomolecular alterations, which can be focused for further mechanistic investigations.

中文翻译：

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爱泼斯坦-巴尔病毒影响下脑微血管内皮细胞的早期生物分子变化：拉曼显微镜研究。

脑微血管内皮细胞 (EC) 在保护大脑免受有害病原体侵害方面发挥着重要作用。然而，一些病毒病原体可以巧妙地调节内皮通路进入大脑。此外，这些病毒会导致内皮功能障碍，从而导致严重的神经系统疾病。爱泼斯坦-巴尔病毒 (EBV) 是一种致癌病毒，也与各种神经系统疾病有关。该病毒主要感染上皮细胞和 B 细胞，然而，它也有感染 EC 并引起内皮激活的倾向。然而，EBV 对 EC 的影响仍未得到充分探索。研究病毒介导的细胞调节的早期事件有助于了解病毒的感染策略或后果。拉曼显微光谱已广泛用于生物医学科学以破译细胞变化。为了通过研究早期时间点的细胞内生物分子变化来了解 EBV 影响的 EC 调制，我们使用了拉曼显微光谱工具。我们用 EBV 处理 EC，并在不同时间点（2、4、6、12、24 和 36 小时）和不同部位（细胞核和外围）获取拉曼光谱，以检查与特定生物分子相关的拉曼强度的变化。在 EBV 处理的细胞中，与未感染的细胞相比，观察到各种生物分子在拉曼强度方面的状态发生了变化。具体而言，胆固醇、多糖、核苷酸、核酸和脯氨酸部分在不同时间点发生了变化。我们还使用分子网络分析研究了这些分子之间可能的相关性，并观察了各种相关因素。这些因素可能会受到 EBV 的影响，从而改变相关的生物分子水平。我们的研究为研究人脑微血管 EC 中的 EBV 感染铺平了道路，并强调了特定的生物分子改变，可以集中用于进一步的机制研究。