Dobrava-Belgrade hantavirus from Germany shows receptor usage and innate immunity induction consistent with the pathogenicity of the virus in humans

• Published in: PloS one 2012-04, Vol.7 (4), p.e35587-e35587
• Main Authors: Popugaeva, Elena, Witkowski, Peter T, Schlegel, Mathias, Ulrich, Rainer G, Auste, Brita, Rang, Andreas, Krüger, Detlev H, Klempa, Boris
• Format: Article
• Language: English
• Subjects: Acids; Analysis; Animals; Antibodies; Apodemus; Apodemus agrarius; Apodemus flavicollis; Biological response modifiers; Biology; Cell culture; Cell Line; Cercopithecus aethiops; CHO Cells; Clustering; Cricetinae; Decay-accelerating factor; Fever; Gene expression; Genetic aspects; Genome, Viral; Germany; Hantavirus; Hantavirus - genetics; Hantavirus - immunology; Hantavirus - isolation & purification; Hantavirus - pathogenicity; Health aspects; Hemorrhage; Hemorrhagic fever with renal syndrome; Hemorrhagic Fever with Renal Syndrome - immunology; Hemorrhagic Fever with Renal Syndrome - virology; Hemorrhagic fevers; Human behavior; Humans; Immunity; Immunity, Innate; Infectious diseases; Innate immunity; Integrins; Interferon; Interferons - immunology; Kidneys; Lungs; Mathematical models; Mediation; Medical schools; Medicine; Mice; Nucleotide sequence; Pathogenesis; Pathogenicity; Pathogens; Phylogenetics; Phylogeny; Proteins; Receptors; Vero Cells; Virology; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0035587

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. 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. 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.