Institute of Biochemistry II, Faculty of Medicine, Goethe University, Frankfurt am Main, Germany.
Institute of Virology, Philipps University Marburg, Marburg, Germany.
Life Sci Alliance. 2022 Feb 2;5(5). doi: 10.26508/lsa.202201371. Print 2022 May.
Acute kidney injury is associated with mortality in COVID-19 patients. However, host cell changes underlying infection of renal cells with SARS-CoV-2 remain unknown and prevent understanding of the molecular mechanisms that may contribute to renal pathology. Here, we carried out quantitative translatome and whole-cell proteomics analyses of primary renal proximal and distal tubular epithelial cells derived from human donors infected with SARS-CoV-2 or MERS-CoV to disseminate virus and cell type-specific changes over time. Our findings revealed shared pathways modified upon infection with both viruses, as well as SARS-CoV-2-specific host cell modulation driving key changes in innate immune activation and cellular protein quality control. Notably, MERS-CoV infection-induced specific changes in mitochondrial biology that were not observed in response to SARS-CoV-2 infection. Furthermore, we identified extensive modulation in pathways associated with kidney failure that changed in a virus- and cell type-specific manner. In summary, we provide an overview of the effects of SARS-CoV-2 or MERS-CoV infection on primary renal epithelial cells revealing key pathways that may be essential for viral replication.
急性肾损伤与 COVID-19 患者的死亡率相关。然而,SARS-CoV-2 感染肾细胞的宿主细胞变化尚不清楚,这阻碍了对可能导致肾病理的分子机制的理解。在这里,我们对来自人类供体的原代肾近端和远端肾小管上皮细胞进行了定量翻译组学和全细胞蛋白质组学分析,以传播病毒并随时间推移观察细胞类型特异性变化。我们的研究结果揭示了两种病毒感染后共同修饰的途径,以及 SARS-CoV-2 特异性宿主细胞调节,驱动固有免疫激活和细胞蛋白质质量控制的关键变化。值得注意的是,MERS-CoV 感染诱导的线粒体生物学的特定变化在 SARS-CoV-2 感染中没有观察到。此外,我们还发现与肾衰竭相关的途径发生了广泛的调节,这些调节以病毒和细胞类型特异性的方式发生。总之,我们提供了 SARS-CoV-2 或 MERS-CoV 感染对原代肾上皮细胞的影响概述,揭示了可能对病毒复制至关重要的关键途径。