Hantavirus infection is an acute zoonosis that clinically manifests in two primary forms, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). HFRS is endemic in Europe and Russia, where the mild form of the disease is prevalent in the Tatarstan region. HPS is endemic in Argentina, as well as other countries of North and South American. HFRS and HPS are usually acquired via the upper respiratory tract by inhalation of virus-contaminated aerosol. Although the pathogenesis of HFRS and HPS remains largely unknown, postmortem tissue studies have identified endothelial cells as the primary target of infection. Importantly, cell damage due to virus replication, or subsequent tissue repair, has not been documented. Since no single factor has been identified that explains the complexity of HFRS or HPS pathogenesis, it has been suggested that a cytokine storm may play a crucial role in the manifestation of both diseases. In order to identify potential serological markers that distinguish HFRS and HPS, serum samples collected during early and late phases of the disease were analyzed for 48 analytes using multiplex magnetic bead-based assays. Overall, serum cytokine profiles associated with HPS revealed a more pro-inflammatory milieu as compared to HFRS. Furthermore, HPS was strictly characterized by the upregulation of cytokine levels, in contrast to HFRS where cases were distinguished by a dichotomy in serum cytokine levels. The severe form of hantavirus zoonosis, HPS, was characterized by the upregulation of a higher number of cytokines than HFRS (40 vs 21). In general, our analysis indicates that, although HPS and HFRS share many characteristic features, there are distinct cytokine profiles for these diseases. These profiles suggest a strong activation of an innate immune and inflammatory responses are associated with HPS, relative to HFRS, as well as a robust activation of Th1-type immune responses. Finally, the results of our analysis suggest that serum cytokines profiles of HPS and HFRS cases are consistent with the presence of extracellular matrix degradation, increased mononuclear leukocyte proliferation, and transendothelial migration.

Serum cytokine profiles differentiating hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome

Hantavirus nephropathy (CVI) is considered to be acute kidney injury (AKI) associated with hantavirus infection (CVI). This infection in the countries of the European and Asian continents causes hemorrhagic fever with renal syndrome (HFRS). However, up to 60% of kidney damage is manifested by pathological changes in urinary sediment without signs of AKI, in connection with which the problems of terminology and diagnosis of kidney damage in HFRS were discussed. A review of the world literature of recent years, devoted to the study of modern data on the pathogenesis of CVI, is presented. The data were revealed that explain the organ specificity of the pathological process in different variants of CVI. The data were revealed that explain the organ specificity of the pathological process in different variants of CVI. The mechanisms related to various aspects of the pathogenesis of hantavirus nephropathy are considered. The factors that alter the functional activity of target cells through the direct action of the virus and the factors mediated by the immune response of the biological host to viral proteins in the form of the action of cytokines ("cytokine storm") causing damage to target organs (indirect factors) are listed. The influence of the hantavirus serotype, genetic factors, and the nature of the immune response of the biological host organism on the severity of renal dysfunction was shown. The concept of "acute damage to podocytes" is disclosed, which explains massive protein uria at the onset of the disease. The molecular and cellular mechanisms of damage to the main compartments of the kidney during hantavirus infection are presented. Disorders of hemostasis and mechanisms of hypercoagulation were demonstrated that underlie glomerular AKI due to acute microvascular syndrome, which is realized in the form of disseminated intravascular coagulation (DIC), hemolytic uremic syndrome (HUS), and thrombotic microangiopathy (TMA). The results of experimental data obtained on a laboratory model of infection and in cell culture, histological studies of autopsy material, and nephrobiopsy specimens from patients with hantavirus nephropathy are demonstrated.

A. N. Kovalenko

Papers

Contemporary view about the pathogenesis of Hantavirus nephropathy (Literature rewiew)