Orthohantaviruses are rodent-borne emerging viruses that may cause severe diseases in humans but no apparent pathology in their small mammal reservoirs. However, the mechanisms leading to tolerance or pathogenicity in humans and persistence in rodent reservoirs are poorly understood, as is the manner in which they spread within and between organisms. Here, we used a range of cellular and molecular approaches to investigate the interactions of three different orthohantaviruses-Puumala virus (PUUV), responsible for a mild to moderate form of hemorrhagic fever with renal syndrome in humans, Tula virus (TULV) with low pathogenicity, and non-pathogenic Prospect Hill virus (PHV)-with human and rodent host cell lines. Besides the fact that cell susceptibility to virus infection was shown to depend on the cell type and virus strain, the three orthohantaviruses were able to infect Vero E6 and HuH7 human cells, but only the former secreted infectious particles. In cells derived from PUUV reservoir, the bank vole (Myodes glareolus), PUUV achieved a complete viral cycle, while TULV did not enter the cells and PHV infected them but did not produce infectious particles, reflecting differences in host specificity. A search for mature virions by electron microscopy (EM) revealed that TULV assembly occurred in part at the plasma membrane, whereas PHV particles were trapped in autophagic vacuoles in cells of the heterologous rodent host. We described differential interactions of orthohantaviruses with cellular factors, as supported by the cellular distribution of viral nucleocapsid protein with cell compartments, and proteomics identification of cellular partners. Our results also showed that interferon (IFN) dependent gene expression was regulated in a cell and virus species dependent manner. Overall, our study highlighted the complexity of the host-virus relationship and demonstrated that orthohantaviruses are restricted at different levels of the viral cycle. In addition, the study opens new avenues to further investigate how these viruses differ in their interactions with cells to evade innate immunity and how it depends on tissue type and host species.
- MeSH
- Arvicolinae MeSH
- Hantavirus * genetika MeSH
- hlodavci MeSH
- interferony MeSH
- lidé MeSH
- nukleokapsida - proteiny genetika MeSH
- RNA-viry * MeSH
- virus Puumala * genetika MeSH
- viry * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- interferony MeSH
- nukleokapsida - proteiny MeSH
Puumala virus (PUUV), carried by bank voles (Myodes glareolus), is the medically most important hantavirus in Central and Western Europe. In this study, a total of 523 bank voles (408 from Germany, 72 from Slovakia, and 43 from Czech Republic) collected between the years 2007-2012 were analyzed for the presence of hantavirus RNA. Partial PUUV genome segment sequences were obtained from 51 voles. Phylogenetic analyses of all three genome segments showed that the newfound strains cluster with other Central and Western European PUUV strains. The new sequences from Šumava (Bohemian Forest), Czech Republic, are most closely related to the strains from the neighboring Bavarian Forest, a known hantavirus disease outbreak region. Interestingly, the Slovak strains clustered with the sequences from Bohemian and Bavarian Forests only in the M but not S segment analyses. This well-supported topological incongruence suggests a segment reassortment event or, as we analyzed only partial sequences, homologous recombination. Our data highlight the necessity of sequencing all three hantavirus genome segments and of a broader bank vole screening not only in recognized endemic foci but also in regions with no reported human hantavirus disease cases.
- Klíčová slova
- Central Europe, Hantavirus, Homologous recombination, Myodes glareolus, Puumala orthohantavirus, Reassortment,
- MeSH
- Arvicolinae virologie MeSH
- fylogeneze MeSH
- genotyp MeSH
- hantavirové infekce virologie MeSH
- Hantavirus genetika MeSH
- lidé MeSH
- molekulární evoluce MeSH
- RNA virová genetika MeSH
- virus Puumala genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
- Evropa MeSH
- Německo MeSH
- Slovenská republika MeSH
- Názvy látek
- RNA virová MeSH
Endemic regions for Puumala virus (PUUV) are located in the most affected federal state Baden-Wuerttemberg, South-West Germany, where high numbers of notified human hantavirus disease cases have been occurring for a long time. The distribution of human cases in Baden-Wuerttemberg is, however, heterogeneous, with a high number of cases recorded during 2012 in four districts (H districts) but a low number or even no cases recorded in four other districts (L districts). Bank vole monitoring during 2012, following a beech (Fagus sylvatica) mast year, resulted in the trapping of 499 bank voles, the host of PUUV. Analyses indicated PUUV prevalences of 7-50% (serological) and 1.8-27.5% (molecular) in seven of eight districts, but an absence of PUUV in one L district. The PUUV prevalence differed significantly between bank voles in H and L districts. In the following year 2013, 161 bank voles were trapped, with reduced bank vole abundance in almost all investigated districts except one. In 2013, no PUUV infections were detected in voles from seven of eight districts. In conclusion, the linear modelling approach indicated that the heterogeneous distribution of human PUUV cases in South-West Germany was caused by different factors including the abundance of PUUV RNA-positive bank voles, as well as by the interaction of beech mast and the proportional coverage of beech and oak (Quercus spec.) forest per district. These results can aid developing local public health risk management measures and early warning models.
- Klíčová slova
- Germany, Hantavirus, bank vole, endemic region, incidence, prevalence,
- MeSH
- Arvicolinae krev virologie MeSH
- ekosystém MeSH
- hemoragická horečka s renálním syndromem epidemiologie MeSH
- lidé MeSH
- Murinae MeSH
- protilátky virové krev MeSH
- rizikové faktory MeSH
- RNA virová izolace a purifikace MeSH
- roční období MeSH
- virus Puumala * MeSH
- zdroje nemoci virologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Německo epidemiologie MeSH
- Názvy látek
- protilátky virové MeSH
- RNA virová MeSH
Hantaviruses are RNA viruses of the Bunyaviridae family, represented in the Czech Republic by three genospecies: Dobrava-Belgrade, Puumala and Tula. They persist in natural foci of infection. In 2004 to 2009, a local outbreak with 18 reported cases of nephropathia epidemica caused by Puumala hantavirus occurred in the Sumava mountains and foothills and was spacially associated with another outbreak in Lower Bavaria, Germany. In the Jeleni locality in the Sumava mountains at 880 m above sea level, we identified a natural focus of infection suspected to be the source of hantavirus infection in forest workers. The focus was characterized geobotanically as a montane mixed forest with the predominance of beeches within the association Dentario enneaphylli-Fagetum, alliance Fagion, sub-alliance Eu-Fagenion, in a cold climate region with a podzolic soil. The biocenoses where hantaviruses are circulating typically show higher microclimate humidity. Their characteristization can be helpful in predicting where hantaviruses are likely to circulate.
- MeSH
- Arvicolinae * MeSH
- ekosystém MeSH
- epidemický výskyt choroby * MeSH
- hemoragická horečka s renálním syndromem epidemiologie veterinární MeSH
- lidé MeSH
- nemoci hlodavců epidemiologie virologie MeSH
- prevalence MeSH
- surveillance populace MeSH
- virus Puumala izolace a purifikace MeSH
- zdroje nemoci veterinární virologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika epidemiologie MeSH
In 1998 - 2008, serum samples from 464 patients, predominantly residents of the Moravia-Silesian Region, were examined in the Department of Virology, Public Health Institute in Ostrava, using Enzyme-Linked ImmunoSorbent Assay (ELISA) for the detection of specific anti-hantavirus antibodies. Seropositivity was ascertained in 41 persons (8.8%). More patients tested seropositive against Hantaan virus (24, i.e. 58.5%) than against Puumala virus (13, i.e. 31.7%). Four persons were reactive against both antigens. Clinical symptoms corresponding to hantavirus infection were observed in 19 seropositive patients. Fifteen of them had antibodies reactive with Hantaan virus antigen (cross-reactive with anti-Dobrava virus), 3 patients had antibodies against Puumala virus and 1 patient had both types of antibodies. Clinical data on the other seropositive persons were lacking. The higher rate of Dobrava virus infections in the Moravian-Silesian Region seems to be associated, among others, with the geographic distribution of striped field mouse (Apodemus agrarius) which is the main reservoir of Dobrava virus in Central Europe.
- MeSH
- dítě MeSH
- dospělí MeSH
- hantavirové infekce diagnóza epidemiologie MeSH
- Hantavirus imunologie MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- předškolní dítě MeSH
- protilátky virové krev MeSH
- séroepidemiologické studie MeSH
- virus Puumala imunologie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- Názvy látek
- protilátky virové MeSH
The first three children with Puumala virus nephropathy diagnosis in the Czech Republic are reported on. A boy and two girls were admitted with symptoms of interstitial nephritis. The medical history in all children revealed flu-like symptoms. All patients were mildly pyrexial and had elevated erythrocytes sedimentation rate, C-reactive protein and low hemoglobin levels. Serum creatinine levels were elevated and proteinuria exceeded 700 mg/L in all children. Tubular proteinuria, glycosuria, high urinary N-acetyl-beta-D-glucosaminidase levels and alpha-1-microglobulin levels confirmed the tubular lesion. Renal biopsies revealed a uniform pattern and showed non-purulent interstitial nephritis in all patients. Puumala virus antigen antibodies were detected in the plasma. All patients were treated with steroids and urine abnormalities and renal function returned to normal within 4 weeks. Hantavirus infection should be considered as one of possible causes of interstitial nephritis with decreased GFR in children even in areas with a low incidence of this infection.
- MeSH
- diferenciální diagnóza MeSH
- dítě MeSH
- hantavirové infekce diagnóza epidemiologie MeSH
- Hantavirus * MeSH
- hemoragická horečka s renálním syndromem diagnóza patofyziologie MeSH
- lidé MeSH
- mladiství MeSH
- progrese nemoci MeSH
- virus Puumala * MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
