Dobrava-belgrade virus spillover infections, Germany.
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ABSTRACT:
SUBMITTER: Schlegel M
PROVIDER: S-EPMC3044545 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: Not available
| S-EPMC3204779 | biostudies-literature
Project description:In 2009, human Dobrava-Belgrade virus (DOBV) infections were reported on the Black Sea coast of Turkey. Serologic and molecular studies of potential rodent reservoirs demonstrated DOBV infections in Apodemus flavicollis and A. uralensis mice. Phylogenetic analysis of DOBV strains showed their similarity to A. flavicollis mice-borne DOBV in Greece, Slovenia, and Slovakia.
| S-EPMC3887490 | biostudies-literature
Project description: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. METHODOLOGY/PRINCIPAL FINDINGS: 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 ?3 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 ? and ? 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/SIGNIFICANCE: 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.
| S-EPMC3335829 | biostudies-literature
Project description:We used an in vitro model to study the impact of hantavirus infection on the cellular gene expression profile. To do so, A549 cells were infected with pathogenic DOBV genotypes Dobrava, Kurkino, and Sochi and less-pathogenic TULV . A549 cells were chosen because of their high susceptibility towards hantavirus infection and because many fundamental studies on hantavirus biology and on host gene expression changes following infection have been performed with this cell line. Cells were infected at a high multiplicity of infection of 5 focus forming units (FFU) per cell to guarantee uniform infection of all cells. Total RNA from infected and mock-infected control cells was isolated at 12 h post infection. This point of time was chosen to allow enough time for establishment of infection and progression to early viral gene expression but to avoid the risk of missing gene expression changes associated with the onset of the cellular innate immune response towards infection. The distinct modulation of cellular transcription of A549 cells was analyzed by means of a whole genome cRNA microarray. All experiments were performed in duplicate using RNA samples from two independently infected cell cultures for each analysis. To compare the gene expression profiles, ratios were calculated by dividing the merged normalized signal intensities of infected samples by mock-control signal intensities. Genes that exhibited a ≥2-fold change (FC) in gene expression and signal intensities that were significantly above the background with p-values ≤ 0.01 were chosen for further analysis. The successful infection of A549 cells with all viruses and the uniform progression of infection were confirmed by immunofluorescence microscopy of cells infected in parallel. At 12 h post infection with each virus nearly all cells were infected without showing cytopathic effects. Since different clinical courses are caused by infection with distinct DOBV genotypes, genotype-specific regulation of cellular transcripts were investigated that may be crucial for pathogenesis in vitro. Selected infection regulated candidates were verified by qPCR at different time points after infection.
2015-11-01 | GSE73410 | GEO
Project description:Acute kidney injury (AKI) caused by hantavirus infections is rare but should be suspected in any patient presenting with flu-like symptoms, signs of haemolytic-uraemic syndrome or presence of anti-glomerular basement membrane (anti-GBM) antibodies. We report the first case of Dobrava-Belgrade virus in France imported from southeastern Europe. The characteristic macroscopic appearance of the fresh renal biopsy specimen, displaying a haemorrhagic appearance of the medulla, suggested hantavirus infection. AKI caused by hantavirus infections remains a diagnostic challenge, especially outside endemic areas.
| S-EPMC7986331 | biostudies-literature
Project description:We used an in vitro model to study the impact of hantavirus infection on the cellular gene expression profile. To do so, A549 cells were infected with pathogenic DOBV genotypes Dobrava, Kurkino, and Sochi and less-pathogenic TULV . A549 cells were chosen because of their high susceptibility towards hantavirus infection and because many fundamental studies on hantavirus biology and on host gene expression changes following infection have been performed with this cell line. Cells were infected at a high multiplicity of infection of 5 focus forming units (FFU) per cell to guarantee uniform infection of all cells. Total RNA from infected and mock-infected control cells was isolated at 12 h post infection. This point of time was chosen to allow enough time for establishment of infection and progression to early viral gene expression but to avoid the risk of missing gene expression changes associated with the onset of the cellular innate immune response towards infection. The distinct modulation of cellular transcription of A549 cells was analyzed by means of a whole genome cRNA microarray. All experiments were performed in duplicate using RNA samples from two independently infected cell cultures for each analysis. To compare the gene expression profiles, ratios were calculated by dividing the merged normalized signal intensities of infected samples by mock-control signal intensities. Genes that exhibited a â¥2-fold change (FC) in gene expression and signal intensities that were significantly above the background with p-values ⤠0.01 were chosen for further analysis. The successful infection of A549 cells with all viruses and the uniform progression of infection were confirmed by immunofluorescence microscopy of cells infected in parallel. At 12 h post infection with each virus nearly all cells were infected without showing cytopathic effects. Since different clinical courses are caused by infection with distinct DOBV genotypes, genotype-specific regulation of cellular transcripts were investigated that may be crucial for pathogenesis in vitro. Selected infection regulated candidates were verified by qPCR at different time points after infection. We analyzed the gene expression profile of A549 cells wich were either mock-infected or infected with Dobrava Virus (DOBV) Dobrava, Kurkino or Sochi, or with Tula Virus (TULV) at a multiplicity of infection of 5. Experiments were performed in duplicate. At 12 h post infection total RNA was isolated from infected cells and used for microarray analysis.
2015-11-01 | E-GEOD-73410 | biostudies-arrayexpress
Project description:Dobrava-Belgrade virus (DOBV) is a human pathogen that has evolved in, and is hosted by, mice of several species of the genus Apodemus. We propose a subdivision of the species Dobrava-Belgrade virus into four related genotypes - Dobrava, Kurkino, Saaremaa, and Sochi - that show characteristic differences in their phylogeny, specific host reservoirs, geographical distribution, and pathogenicity for humans.
| S-EPMC3586401 | biostudies-literature
Project description:A survey of 158 rodents caught in the Czech Republic identified Dobrava virus sequences closely related to that of the Dobrava virus type strain in Apodemus sylvaticus and Mus musculus rodents. The identity of A. sylvaticus was unequivocally confirmed by random amplified polymorphic DNA analysis. The data seem to indicate hantavirus spillover from Apodemus flavicollis to other rodents.
| S-EPMC548048 | biostudies-literature
Project description:Hantavirus disease belongs to the emerging infections. The clinical picture and severity of infections differ between hantavirus species and may even vary between hantavirus genotypes. The mechanisms that lead to the broad variance of severity in infected patients are not completely understood. Host- and virus-specific factors are considered.We analyzed severe cases of hantavirus disease in two young women. The first case was caused by Puumala virus (PUUV) infection in Germany; the second case describes the infection with Dobrava-Belgrade virus (DOBV) in Russia. Symptoms, laboratory parameters and cytokine levels were analyzed and compared between the two patients. Serological and sequence analysis revealed that PUUV was the infecting agent for the German patient and the infection of the Russian patient was caused by Dobrava-Belgrade virus genotype Sochi (DOBV-Sochi). The symptoms in the initial phase of the diseases did not differ noticeably between both patients. However, deterioration of laboratory parameter values was prolonged and stronger in DOBV-Sochi than in PUUV infection. Circulating endothelial progenitor cells (cEPCs), known to be responsible for endothelial repair, were mobilized in both infections. Striking differences were observed in the temporal course and level of cytokine upregulation. Levels of angiopoietin-2 (Ang-2), vascular endothelial growth factor (VEGF), and stromal derived factor-1 (SDF-1?) were increased in both infections; but, sustained and more pronounced elevation was observed in DOBV-Sochi infection.Severe hantavirus disease caused by different hantavirus species did not differ in the general symptoms and clinical characteristics. However, we observed a prolonged clinical course and a late and enhanced mobilization of cytokines in DOBV-Sochi infection. The differences in cytokine deregulation may contribute to the observed variation in the clinical course.
| S-EPMC5109704 | biostudies-literature
Project description:Approximately 60% of hepatitis A virus infections in Germany occur in persons without a travel history to disease-endemic areas and for whom sources of infection are unknown. Recommendation of pretravel vaccination fails to prevent the remaining imported infections. Using enhanced surveillance in 2007-2008, we analyzed epidemiologic patterns of hepatitis A in Germany and appropriateness and adequacy of current immunization recommendations. Young patients with a migration background who had visited friends and family in their ancestral countries accounted for most imported cases. Phylogenetic analysis showed high diversity of sequence data and clustering of strains with similar regions of origin or patient migration backgrounds. Virologic findings are compatible with those of low-incidence countries, where virtually all infections are directly or indirectly imported from other regions. Germans with a migration background are seen as a special risk group so far insufficiently reached by pretravel vaccination advice.
| S-EPMC2857222 | biostudies-literature