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体外肾上皮细胞感染揭示了病毒对肾脏的趋向性,这可能是中东呼吸综合征冠状病毒感染导致急性肾衰竭的机制之一。

In-vitro renal epithelial cell infection reveals a viral kidney tropism as a potential mechanism for acute renal failure during Middle East Respiratory Syndrome (MERS) Coronavirus infection.

机构信息

Institute of Virology, University of Bonn Medical Centre, Sigmund-Freud-Strasse 25, Bonn 53127, Germany.

出版信息

Virol J. 2013 Dec 23;10:359. doi: 10.1186/1743-422X-10-359.

Abstract

BACKGROUND

The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes symptoms similar to Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), yet involving an additional component of acute renal failure (ARF) according to several published case reports. Impairment of the kidney is not typically seen in Coronavirus infections. The role of kidney infection in MERS is not understood.

FINDINGS

A systematic review of communicated and peer-reviewed case reports revealed differences in descriptions of kidney involvement in MERS versus SARS patients. In particular, ARF in MERS patients occurred considerably earlier after a median time to onset of 11 days (SD ±2,0 days) as opposed to 20 days for SARS, according to the literature. In-situ histological staining of the respective cellular receptors for MERS- and SARS-Coronavirus showed highly similar staining patterns with a focus of a receptor-specific signal in kidney epithelial cells. Comparative infection experiments with SARS- and MERS-CoV in primary human kidney cells versus primary human bronchial epithelial cells showed cytopathogenic infection only in kidney cells, and only if infected with MERS-CoV. Kidney epithelial cells produced almost 1000-fold more infectious MERS-CoV progeny than bronchial epithelial cells, while only a small difference was seen between cell types when infected with SARS-CoV.

CONCLUSION

Epidemiological studies should analyze kidney impairment and its characteristics in MERS-CoV. Virus replication in the kidney with potential shedding in urine might constitute a way of transmission, and could explain untraceable transmission chains leading to new cases. Individual patients might benefit from early induction of renoprotective treatment.

摘要

背景

中东呼吸综合征冠状病毒(MERS-CoV)引起的症状与严重急性呼吸综合征冠状病毒(SARS-CoV)相似,但根据几项已发表的病例报告,还涉及急性肾衰竭(ARF)的额外成分。冠状病毒感染通常不会损害肾脏。MERS 中肾脏感染的作用尚不清楚。

发现

对已沟通和同行评审的病例报告进行的系统审查显示,MERS 与 SARS 患者的肾脏受累描述存在差异。特别是,MERS 患者的 ARF 发生时间明显更早,中位发病时间为 11 天(标准差±2.0 天),而 SARS 为 20 天。对 MERS-和 SARS-CoV 的相应细胞受体的原位组织学染色显示出高度相似的染色模式,在肾脏上皮细胞中受体特异性信号集中。用 SARS-CoV 和 MERS-CoV 在原代人肾细胞与原代人支气管上皮细胞中的比较感染实验表明,仅在肾细胞中发生细胞病变性感染,并且仅在感染 MERS-CoV 时才发生感染。肾上皮细胞产生的传染性 MERS-CoV 子代比支气管上皮细胞多近 1000 倍,而在用 SARS-CoV 感染时,细胞类型之间仅观察到微小差异。

结论

应在 MERS-CoV 中分析肾脏损害及其特征的流行病学研究。肾脏中的病毒复制并可能在尿液中排出可能构成一种传播方式,并可以解释导致新病例的无法追踪的传播链。个别患者可能受益于早期诱导肾保护治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a52/3878046/3f1063e9b909/1743-422X-10-359-1.jpg

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