Boegelein Lukas, Schreiber Pamela, Philipp Alexandra, Nusshag Christian, Essbauer Sandra, Zeier Martin, Krautkrämer Ellen
Department of Nephrology, University of Heidelberg, Im Neuenheimer Feld 162, D-69120, Heidelberg, Germany.
Department Virology and Intracellular Agents, Bundeswehr Institute of Microbiology, German Centre for Infection Research, Munich Partner Site, D-80937, Munich, Germany.
Virol J. 2024 Oct 1;21(1):241. doi: 10.1186/s12985-024-02517-5.
Eurasian pathogenic orthohantaviruses cause hemorrhagic fever with renal syndrome (HFRS) characterized by acute kidney injury (AKI). The virulence of orthohantaviruses varies enormously and direct infection of different renal cell types contribute to pathogenesis. Glomerular mesangial cells play an essential role in the interplay between kidney cells and proper kidney function. Therefore, we analyzed the replication competence of different orthohantavirus species in primary mesangial cells and a mesangial cell line.
We tested the suitability of the mesangial cell line CIHGM-1 (conditionally immortalized human glomerular mesangial cells) as cell culture model for orthohantavirus kidney infection by comparison with primary human renal mesangial cells (HRMCs). We analyzed infection with high pathogenic Hantaan virus (HTNV), moderate pathogenic Puumala virus (PUUV) and non-/low-pathogenic Tula virus (TULV).
Effective viral spread was observed for PUUV only, whereas infection with HTNV and TULV was abortive. However, in contrast to TULV, HTNV exhibits an initially high infection rate and declines afterwards. This replication pattern was observed in HRMCs and CIHGM-1 cells. Viability or adhesion was neither impaired for PUUV-infected CIHGM-1 nor HRMCs. A loss of migration capacity was observed in PUUV-infected CIHGM-1 cells, but not in HRMCs.
The identification of differences in the replication competence of pathogenic orthohantavirus strains in renal mesangial cells is of special interest and may provide useful insights in the virus-specific mechanisms of orthohantavirus induced AKI. The use of CIHGM-1 cells will facilitate the research in a relevant cell culture system.
欧亚致病性汉坦病毒引起以急性肾损伤（AKI）为特征的肾综合征出血热（HFRS）。汉坦病毒的毒力差异极大，不同肾细胞类型的直接感染参与发病机制。肾小球系膜细胞在肾细胞间相互作用及正常肾功能中起重要作用。因此，我们分析了不同汉坦病毒种类在原代系膜细胞和系膜细胞系中的复制能力。
通过与原代人肾系膜细胞（HRMCs）比较，测试系膜细胞系CIHGM-1（条件永生化人肾小球系膜细胞）作为汉坦病毒肾感染细胞培养模型的适用性。我们分析了高致病性汉坦病毒（HTNV）、中度致病性普马拉病毒（PUUV）和非/低致病性图拉病毒（TULV）的感染情况。
仅观察到PUUV有有效的病毒传播，而HTNV和TULV的感染是流产性的。然而，与TULV不同，HTNV最初感染率较高，随后下降。这种复制模式在HRMCs和CIHGM-1细胞中均有观察到。PUUV感染的CIHGM-1细胞和HRMCs的活力或黏附均未受损。在PUUV感染的CIHGM-1细胞中观察到迁移能力丧失，但在HRMCs中未观察到。
鉴定致病性汉坦病毒株在肾系膜细胞中复制能力的差异具有特殊意义，可能为汉坦病毒诱导的AKI的病毒特异性机制提供有用的见解。CIHGM-1细胞的使用将有助于在相关细胞培养系统中进行研究。
