[Immunopathogenesis of hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome].

Hantaviruses (HTV) cause two serious human diseases: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS), posing a considerable public health problem worldwide. Immunopathogenesis has been suggested to be involved in both HFRS and HPS. A common feature of hantavirus diseases is an increased microvascular bed permeability, suggesting that vascular endothelium is a prime target of virus infection. Although HTV infect numerous cell lines and primary cells, it was considered that they do cause no cytopathic effect. Recently, we found HTV to cause a cytopathic effect and apoptosis in 293 HEK cells. Monocytes/macrophages also represent the important target cells, which may also have an important role in the spread of HTV from the primary site of infection. Both endothelial cells and monocytes/macrophages may act as a rich source of cytokines/chemokines during the infection with HTV and additionally contribute to the HFRS/HPS immunopathogenesis. The main reservoirs of HTV are small rodents which are infected but do not have manifest disease. However, some studies show that T-lymphocytes may play an important role in rodent resistance to infection with HTV. Some clinical studies indicate the important role of pro-inflammatory cytokines in the immunopathogenesis of HFRS/HPS. The efficient anti-hantaviral cell-immune response in patients is mainly due to the generation of cytotoxic T-lymphocytes. Our study also pointed to a decrease in the percentage of total naive (CD45RA) cells and an increase in the percentage of memory cells (CD45RO). Specific IgM antibodies appear at the very beginning of the diseases followed by an increase in specific IgG. Additionally, IgE antibodies have been suggested to play a role in HFRS immunopathogenesis. Immune complexes have been detected in the sera, on the surface of red blood cells and platelets, in urine, glomerull and dermal capillaries of HFRS patients. They may be responsible for increased capillary permeability, vascular injury, platelet lysis and kidney damage. The immunopathologic disorders accompanying HFRS/HPS are complex. As there is no appropriate animal model to investigate HFRS/HPS immunopathogenesis, we mostly rely on in vitro and rare clinical studies. Additional efforts in the research of immunopathogenesis caused by HTV, may contribute to better understanding of HFRS/HPS characteristics and course of disease, and improve the treatment and prevention.