Marburg virus, a member of the Filoviridae, is the causative agent of Marburg virus disease (MVD), a hemorrhagic fever with a case fatality rate of up to 90 %. Acute kidney injury is common in MVD and is associated with increased mortality, but its pathogenesis in MVD remains poorly understood. Interestingly, autopsies show the presence of viral proteins in different parts of the nephron, particularly in proximal tubular cells (PTC). These findings suggest a potential role for the virus in the development of MVD-related kidney injury. To shed light on this effect, we infected primary human PTC with Lake Victoria Marburg virus and conducted transcriptomic analysis at multiple time points. Unexpectedly, infection did not induce marked cytopathic effects in primary tubular cells at 20 and 40 h post infection. However, gene expression analysis revealed robust renal viral replication and dysregulation of genes essential for different cellular functions. The gene sets mainly downregulated in PTC were associated with the targets of the transcription factors MYC and E2F, DNA repair, the G2M checkpoint, as well as oxidative phosphorylation. Importantly, the downregulated factors comprise PGC-1α, a well-known factor in acute and chronic kidney injury. By contrast, the most highly upregulated gene sets were those related to the inflammatory response and cholesterol homeostasis. In conclusion, Marburg virus infects and replicates in human primary PTC and induces downregulation of processes known to be relevant for acute kidney injury as well as a strong inflammatory response.

中文翻译：

---

马尔堡病毒感染的原代近端肾小管细胞的转录组学揭示了免疫反应与能量代谢的负相关性

马尔堡病毒属于丝状病毒科，是马尔堡病毒病 (MVD) 的病原体，这是一种出血热，病死率高达 90%。急性肾损伤在 MVD 中很常见，并且与死亡率增加相关，但其在 MVD 中的发病机制仍知之甚少。有趣的是，尸检显示病毒蛋白存在于肾单位的不同部位，特别是近端肾小管细胞（PTC）。这些发现表明该病毒在 MVD 相关肾损伤的发生中具有潜在作用。为了阐明这种效应，我们用维多利亚湖马尔堡病毒感染了原代人类 PTC，并在多个时间点进行了转录组分析。出乎意料的是，感染后 20 和 40 小时，感染并未在原代肾小管细胞中引起明显的细胞病变效应。然而，基因表达分析揭示了肾病毒的强劲复制和不同细胞功能所必需的基因的失调。 PTC中主要下调的基因组与转录因子MYC和E2F、DNA修复、G2M检查点以及氧化磷酸化的靶标相关。重要的是，下调的因子包括 PGC-1α，这是一种众所周知的急性和慢性肾损伤因子。相比之下，上调程度最高的基因组是与炎症反应和胆固醇稳态相关的基因组。总之，马尔堡病毒在人类原发性 PTC 中感染和复制，并诱导已知与急性肾损伤相关的过程下调以及强烈的炎症反应。