β2 Integrin–mediated systemic release of neutrophil extracellular traps is a novel mechanism of immunopathology associated with hantavirus infection.

No abstract

The function of the kidney with its highly differentiated and specialized cell types is affected by infection with several viruses. Viral infections of the kidney have a negative impact not only on patients undergoing renal transplantation and immunosuppression. Besides the increasing number of patients suffering from HIV-associated nephropathy, another group of viruses infects immunocompetent patients and induces renal failure. Hantaviruses belong nowadays to the emerging zoonoses that increase in number and geographic distribution. The viruses are distributed worldwide in endemic areas and distribution seems to expand. Together with the increase in the number of cases in the last few years, the understanding of epidemiology and pathology has deepened and some concepts had to be changed. Symptoms and mortality vary between species. The classification refers to geographical distribution: New World hantaviruses causing hantavirus cardiopulmonary syndrome (HCPS) and Old World hantaviruses causing hemorrhagic fever with renal syndrome (HFRS). Indeed, in most HFRS cases, the kidney is mainly affected and HCPS is characterized by cardiopulmonary involvement. But the picture of strict organ tropism is changing and reports of pulmonary findings and nonrenal manifestations in infections with Old World hantaviruses are increasing. However, the overall symptoms-vascular alterations and leakage-that are responsible for organ failure are characteristic for all diseases caused by hantaviruses.

The Old World hantaviruses, members of the family Bunyaviridae, cause hemorrhagic fever with renal syndrome (HFRS). Transmission to humans occurs via inhalation of aerosols contaminated with the excreta of infected rodents. The viral antigen is detectable in dendritic cells, macrophages, lymphocytes, and, most importantly, microvascular endothelial cells. However, the site and detailed mechanism of entry of HFRScausing hantaviruses in polarized epithelial cells have not yet been defined. Therefore, this study focused on the entry of the pathogenic hantaviruses Hantaan and Puumala into African green monkey kidney epithelial cells and primary human endothelial cells. The polarized epithelial and endothelial cells were found to be susceptible to hantavirus infection exclusively from the apical surface. Treatment with phosphatidylinositolspecific phospholipase C, which removes glycosylphosphatidylinositol (GPI)-anchored proteins from the cell surface, protects cells from infection, indicating that hantaviruses require a GPI-anchored protein as a cofactor for entry. Decay-accelerating factor (DAF)/CD55 is a GPI-anchored protein of the complement regulatory system and serves as a receptor for attachment to the apical cell surface for a number of viruses. Infection was reduced by the pretreatment of hantaviral particles with human recombinant DAF. Moreover, the treatment of permissive cells with DAF-specific antibody blocked infection. These results demonstrate that the Old World hantaviruses Hantaan and Puumala enter polarized target cells from the apical site and that DAF is a critical cofactor for infection.

The Nef protein of human immunodeficiency virus type 1 is an important factor in AIDS pathogenesis. In addition to downregulating CD4 and major histocompatibility complex class I molecules from the cell surface, as well as increasing virion infectivity, Nef triggers activation of the T-cell receptor (