title: Dobrava-Belgrade hantavirus from Germany shows receptor usage and innate immunity induction consistent with the pathogenicity of the virus in humans.
abstract: BACKGROUND
  Dobrava-Belgrade virus (DOBV) is a European hantavirus causing hemorrhagic fever with renal syndrome (HFRS) in humans with fatality rates of up to 12%. DOBV-associated clinical cases typically occur also in the northern part of Germany where the virus is carried by the striped field mouse (Apodemus agrarius). However, the causative agent responsible for human illness has not been previously isolated.
  
  
  RESULTS
  Here we report on characterization of a novel cell culture isolate from Germany obtained from a lung tissue of "spillover" infected yellow necked mouse (A. flavicollis) trapped near the city of Greifswald. Phylogenetic analyses demonstrated close clustering of the new strain, designated Greifswald/Aa (GRW/Aa) with the nucleotide sequence obtained from a northern German HFRS patient. The virus was effectively blocked by specific antibodies directed against β3 integrins and Decay Accelerating Factor (DAF) indicating that the virus uses same receptors as the highly pathogenic Hantaan virus (HTNV). In addition, activation of selected innate immunity markers as interferon β and λ and antiviral protein MxA after viral infection of A549 cells was investigated and showed that the virus modulates the first-line antiviral response in a similar way as HTNV.
  
  
  CONCLUSIONS
  In summary, our study reveals novel data on DOBV receptor usage and innate immunity induction in relationship to virus pathogenicity and underlines the potency of German DOBV strains to act as human pathogen.
authors.affiliation: Institute of Virology, Helmut-Ruska-Haus, Charité Medical School, Berlin, Germany.
authors.forename: Elena
authors.initials: E
authors.lastname: Popugaeva
authors.forename: Peter T
authors.initials: PT
authors.lastname: Witkowski
authors.forename: Mathias
authors.initials: M
authors.lastname: Schlegel
authors.forename: Rainer G
authors.initials: RG
authors.lastname: Ulrich
authors.forename: Brita
authors.initials: B
authors.lastname: Auste
authors.forename: Andreas
authors.initials: A
authors.lastname: Rang
authors.forename: Detlev H
authors.initials: DH
authors.lastname: Krüger
authors.forename: Boris
authors.initials: B
authors.lastname: Klempa
mesh_terms: D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D016679:Genome, Viral; D005858:Germany; D006476:Orthohantavirus / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification* / Q000472:pathogenicity; D006480:Hemorrhagic Fever with Renal Syndrome / Q000276:immunology* / Q000821:virology*; D006801:Humans; D007113:Immunity, Innate; D007372:Interferons / Q000276:immunology; D051379:Mice; D010802:Phylogeny; D014709:Vero Cells
chemical_list: D007372:Interferons