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Pathogenesis mechanisms of hantavirus-induced acute renal failure
AG Krautkrämer
Our research focuses on the direct and immune-mediated mechanisms of kidney damage during hantavirus infection.
Pathogenic hantaviruses are transmitted to humans by rodents and can cause various diseases. Species found in the Americas cause hantaviral pulmonary syndrome (HPS), while infection with Eurasian species causes hemorrhagic fever with renal syndrome (HFRS), which is characterized by acute renal failure with high proteinuria. The severity of the disease also varies greatly between species:
The hantavirus Puumala, which is prevalent in Germany, causes a mild form of HFRS with a mortality rate of less than 0.5%, whereas the mortality rate for HFRS caused by infection with Dobrava-Belgrade or Hantaan virus is between 5 and 12%.
The reasons for these differences in organ manifestation and disease severity are not yet understood.
In order to clarify the mechanisms responsible for the kidney-specific clinical picture and the different severity of the disease, we are investigating the replication cycle of different hantavirus species in vitro and analyzing the course of disease in patients with acute hantavirus infection.
We were able to show that Eurasian pathogenic hantaviruses directly infect different cell types of the kidney. Cells of the glomerulus (podocytes, mesangial and endothelial cells) as well as epithelial cells of the tubule are target cells of the viruses.
The infection leads to morphological and functional changes in the infected cells. The observed disruption of cell-cell contacts and deterioration of the adhesion and migration capacity of the cells contribute to the loss of the barrier function of the kidney. These effects are cell type specific, therefore the use of renal human cells as a relevant cell culture system is essential. In contrast, human kidney cells are not permissive for non-pathogenic or low-pathogenic hantaviruses such as tulavirus.
Thus, direct infection of the kidney by pathogenic hantaviruses is a crucial factor in the development of hantavirus-induced renal failure. In addition to these direct effects, we are also investigating the influence of soluble factors on the course of the disease. The analysis of damage markers in serum and urine should reveal signaling pathways that contribute to the disruption of the kidney's barrier function.
Project management
PD Dr. rer. nat. Ellen Krautkrämer
ellen_krautkraemer@med.uni-heidelberg.de
+49 6221 9112 227
Persons involved
Lukas Bögelein (cand. med.)
Ann-Kathrin Friedrich (cand. med. dent.)
Gefion Gruber (cand. med. dent.)
Dr. Christian Nusshag
Pamela Schreiber (M. Sc.)
Josephine Uhrig (TA)