title: Hantavirus causing hemorrhagic fever with renal syndrome enters from the apical surface and requires decay-accelerating factor (DAF/CD55).
abstract: 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 HFRS-causing 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 phosphatidylinositol-specific 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.
authors.affiliation: Department of Nephrology, University of Heidelberg, Im Neuenheimer Feld 162, D-69120 Heidelberg, Germany. ellen_krautkraemer@med.uni-heidelberg.de
authors.forename: Ellen
authors.initials: E
authors.lastname: Krautkrämer
authors.forename: Martin
authors.initials: M
authors.lastname: Zeier
mesh_terms: D000818:Animals; D018958:CD55 Antigens / Q000502:physiology*; D016764:Cell Polarity; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D042783:Endothelial Cells / Q000166:cytology / Q000821:virology; D004730:Endothelium, Vascular / Q000166:cytology / Q000821:virology; D004847:Epithelial Cells / Q000166:cytology / Q000821:virology; D018063:Hantaan virus; D006476:Orthohantavirus / Q000502:physiology*; D006482:Hemorrhagic Fevers, Viral / Q000209:etiology / Q000821:virology*; D006801:Humans; D007674:Kidney Diseases / Q000821:virology; D029262:Puumala virus; D053585:Virus Attachment; D053586:Virus Internalization
chemical_list: D018958:CD55 Antigens