scholarly journals How Bank Vole-PUUV Interactions Influence the Eco-Evolutionary Processes Driving Nephropathia Epidemica Epidemiology—An Experimental and Genomic Approach

Pathogens ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 789
Author(s):  
Sarah Madrières ◽  
Caroline Tatard ◽  
Séverine Murri ◽  
Johann Vulin ◽  
Maxime Galan ◽  
...  
Keyword(s):  
Bank Vole ◽  
Hemorrhagic Fever ◽  
Cross Infection ◽  
Nephropathia Epidemica ◽  
Serological Response ◽  
Mild Form ◽  
Bank Voles ◽  
Genomic Approach ◽  
Endemic Strain ◽  
Excretory Organs

In Europe, Puumala virus (PUUV) is responsible for nephropathia epidemica (NE), a mild form of hemorrhagic fever with renal syndrome (HFRS). Despite the presence of its reservoir, the bank vole, on most of French territory, the geographic distribution of NE cases is heterogeneous and NE endemic and non-endemic areas have been reported. In this study we analyzed whether bank vole-PUUV interactions could partly shape these epidemiological differences. We performed crossed-experimental infections using wild bank voles from French endemic (Ardennes) and non-endemic (Loiret) areas and two French PUUV strains isolated from these areas. The serological response and dynamics of PUUV infection were compared between the four cross-infection combinations. Due to logistical constraints, this study was based on a small number of animals. Based on this experimental design, we saw a stronger serological response and presence of PUUV in excretory organs (bladder) in bank voles infected with the PUUV endemic strain. Moreover, the within-host viral diversity in excretory organs seemed to be higher than in other non-excretory organs for the NE endemic cross-infection but not for the NE non-endemic cross-infection. Despite the small number of rodents included, our results showed that genetically different PUUV strains and in a lesser extent their interaction with sympatric bank voles, could affect virus replication and diversity. This could impact PUUV excretion/transmission between rodents and to humans and in turn at least partly shape NE epidemiology in France.

scholarly journals How bank vole-PUUV interactions influence the eco-evolutionary processes driving nephropathia epidemica epidemiology: An experimental and genomic approach

2020 ◽  
Author(s):  
Sarah Madrières ◽  
Caroline Tatard ◽  
Séverine Murri ◽  
Johann Vulin ◽  
Maxime Galan ◽  
...  
Keyword(s):  
Bank Vole ◽  
Cross Infection ◽  
Nephropathia Epidemica ◽  
Puumala Virus ◽  
Serological Response ◽  
Mild Form ◽  
Bank Voles ◽  
Genomic Approach ◽  
Endemic Strain ◽  
Excretory Organs

AbstractIn Europe, Puumala virus (PUUV) is responsible for nephropathia epidemica (NE), a mild form of haemorrhagic fever with renal syndrome (HFSR). Despite the presence of its reservoir, the bank vole, on most of French territory, the geographic distribution of NE cases is heterogeneous and NE endemic and non-endemic areas have been reported. In this study we analyzed whether bank vole-PUUV interactions could partly shape these epidemiological differences. We performed crossed-experimental infections using wild bank voles from French endemic (Ardennes) and non-endemic (Loiret) areas, and two French PUUV strains isolated from these areas. The serological response and dynamics of PUUV infection were compared between the four cross-infection combinations. We showed that the serological response and the presence of PUUV in excretory organs were more important in bank voles infected with the PUUV endemic strain. Moreover, the within-host viral diversity in excretory organs was higher than in other non-excretory organs for the NE endemic cross-infection, but not for the NE non-endemic cross-infection. Altogether, our results showed that genetically different PUUV strains, and in a lesser extent their interaction with sympatric bank voles, could affect virus replication and diversity. This could impact PUUV excretion/transmission between rodents and to humans, and in turn at least partly shape NE epidemiology in France.

scholarly journals Nephropathia epidemica in Norway: antigen and antibodies in rodent reservoirs and antibodies in selected human populations

1984 ◽  
Vol 93 (1) ◽  
pp. 139-146 ◽  
Author(s):  
T. Traavik ◽  
Ann-Inger Sommer ◽  
R. Mehl ◽  
B. P. Berdal ◽  
K. Stavem ◽  
...  
Keyword(s):  
Bank Vole ◽  
Fluorescent Antibody ◽  
Hemorrhagic Fever ◽  
Nephropathia Epidemica ◽  
Clethrionomys Glareolus ◽  
Distribution Area ◽  
Human Populations ◽  
Fluorescent Antibody Technique ◽  
Antibody Technique ◽  
Bank Voles

SUMMARYNephropathia epidemica (NE) antigen was detected by IFAT (indirect fluorescent antibody technique) in the lungs of 14 of 97 bank voles (Clethrionomys glareolus) collected in three endemic areas. The distribution of antigen positive voles within an endemic location was scattered. Antibodies to Korean hemorrhagic fever (KHF) virus antigens were detected by IFAT in 12 of 14 NE antigen positive bank voles and in 15 of 83 that were antigen negative. NE antigen positive voles exhibited higher antibody titres. Antibodies to KHF were demonstrated in sera from C. rutilus and C. rufocanus collected more than 200 km north of the distribution area for C. glareolus. It appears likely that these vole species can serve as virus vectors for NE cases occurring north of the bank vole area. NE antibodies cross-reacting with KHF virus seem to diminish with time after infection in some NE patients, while for others such cross-reacting antibodies were detected up to 12 years after the disease. Antibodies to KHF were detected in eight of 106 healthy forestry workers with no clinical history of NE. No serological cross-reactions were detected between NE/KHF antigens and representative Bunyaviridae present in Norway. NE/KHF-like viruses appear widespread in Norway, both within and outside of the distribution area of the bank vole.

scholarly journals Detection and Genetic Characterization of Puumala Orthohantavirus S-Segment in Areas of France Non-Endemic for Nephropathia Epidemica

Pathogens ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 721
Author(s):  
Séverine Murri ◽  
Sarah Madrières ◽  
Caroline Tatard ◽  
Sylvain Piry ◽  
Laure Benoit ◽  
...  
Keyword(s):  
Amino Acid ◽  
Bank Vole ◽  
Phylogenetic Analyses ◽  
Hemorrhagic Fever ◽  
Nephropathia Epidemica ◽  
Amino Acid Sequences ◽  
Bank Voles ◽  
History Of ◽  
Endemic Areas

Puumala virus (PUUV) in Europe causes nephropathia epidemica (NE), a mild form of hemorrhagic fever with renal syndrome (HFRS). The incidence of NE is highly heterogeneous spatially, whereas the geographic distribution of the wild reservoir of PUUV, the bank vole, is essentially homogeneous. Our understanding of the processes driving this heterogeneity remains incomplete due to gaps in knowledge. Little is known about the current distribution and genetic variation of PUUV in the areas outside the well-identified zones of NE endemicity. We trapped bank voles in four forests in French regions in which NE is considered non-endemic, but sporadic NE cases have been reported recently. We tested bank voles for anti-PUUV IgG and characterized the S segment sequences of PUUV from seropositive animals. Phylogenetic analyses revealed specific amino-acid signatures and genetic differences between PUUV circulating in non-endemic and nearby NE-endemic areas. We also showed, in temporal surveys, that the amino-acid sequences of PUUV had undergone fewer recent changes in areas non-endemic for NE than in endemic areas. The evolutionary history of the current French PUUV clusters was investigated by phylogeographic approaches, and the results were considered in the context of the history of French forests. Our findings highlight the need to monitor the circulation and genetics of PUUV in a larger array of bank vole populations, to improve our understanding of the risk of NE.

scholarly journals The Distribution of Puumala orthohantavirus Genome Variants Correlates with the Regional Landscapes in the Trans-Kama Area of the Republic of Tatarstan

Pathogens ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1169
Author(s):  
Yuriy N. Davidyuk ◽  
Emmanuel Kabwe ◽  
Anton F. Shamsutdinov ◽  
Anna V. Knyazeva ◽  
Ekaterina V. Martynova ◽  
...  
Keyword(s):  
Bank Vole ◽  
Phylogenetic Analyses ◽  
Genetic Material ◽  
Hemorrhagic Fever ◽  
Federal District ◽  
Genetic Lineage ◽  
Bank Voles ◽  
European Part Of Russia ◽  
The Republic ◽  
River Valleys

In the European part of Russia, the highest number of hemorrhagic fever with renal syndrome (HFRS) cases are registered in the Volga Federal District (VFD), which includes the Republic of Tatarstan (RT). Puumala orthohantavirus (PUUV) is the main causative agent of HFRS identified in the RT. The goal of the current study is to analyze the genetic variations of the PUUV strains and possible presence of chimeric and reassortant variants among the PUUV strains circulating in bank vole populations in the Trans-Kama area of the RT. Complete S segment CDS as well as partial M and L segment coding nucleotide sequences were obtained from 40 PUUV-positive bank voles and used for the analysis. We found that all PUUV strains belonged to RUS genetic lineage and clustered in two subclades corresponding to the Western and Eastern Trans-Kama geographic areas. PUUV strains from Western Trans-Kama were related to the previously identified strain from Teteevo in the Pre-Kama area. It can be suggested that the PUUV strains were introduced to the Teteevo area as a result of the bank voles’ migration from Western Trans-Kama. It also appears that physical obstacles, including rivers, could be overcome by migrating rodents under favorable circumstances. Based on results of the comparative and phylogenetic analyses, we propose that bank vole distribution in the Trans-Kama area occurred upstream along the river valleys, and that watersheds could act as barriers for migrations. As a result, the diverged PUUV strains could be formed in closely located populations. In times of extensive bank vole population growth, happening every 3–4 years, some regions of watersheds may become open for contact between individual rodents from neighboring populations, leading to an exchange of the genetic material between divergent PUUV strains.

scholarly journals First isolation and genetic characterization of Puumala orthohantavirus strains from France

2020 ◽  
Author(s):  
Johann Vulin ◽  
Séverine Murri ◽  
Sarah Madrières ◽  
Maxime Galan ◽  
Caroline Tatard ◽  
...  
Keyword(s):  
Bank Vole ◽  
Endemic Area ◽  
High Throughput Sequencing ◽  
Hemorrhagic Fever ◽  
Amino Acid Sequences ◽  
Myodes Glareolus ◽  
Wild Rodents ◽  
Bank Voles ◽  
A Cell ◽  
The Impact

AbstractPuumala orthohantavirus (PUUV) causes a mild form of hemorrhagic fever with renal syndrome (HFRS) named nephropathia epidemica (NE), regularly diagnosed in Europe. France represents the Western frontier of NE expansion in Europe with two distinct areas: the endemic area (Northeast) where PUUV circulates in rodent populations and where many cases of NE are detected in humans and non-endemic area (Southwest) where the virus is not detected and only a few human cases have been reported. The country is a pertinent target to study factors that influence the evolution of PUUV distribution. In this study, we describe for the first time the isolation of two PUUV strains from two distinct French geographical areas: Ardennes (endemic area) and Loiret (non-endemic area). To isolate PUUV efficiently, we selected wild rodents (Myodes glareolus, the specific reservoir of PUUV) from these areas that were seronegative for anti-PUUV IgG (ELISA) but associated with viral RNA load in lung (qRT-PCR). With this design, we are able to cultivate and maintain these two strains in VeroE6 cells but also to propagate efficiently and rapidly both strains in a bank vole colony. Complete coding sequences of S and M segments were determined by Sanger sequencing of RNA extracted from positive bank voles (naturally and experimentally infected) and from supernatant of Vero E6. For the M segment, nucleotidic sequences were 100% identical for both strains. For the S segment, the amino acid sequences from each strain revealed one mismatch between sequences obtained from tissue and from supernatant, revealing a “bank vole” and a “cell” signature. High throughput sequencing confirmed Sanger results, and provided a better assessment of the impact of isolation methods on intra-host viral diversity.

scholarly journals Microevolution of bank voles (Myodes glareolus) at neutral and immune-related genes during multiannual dynamic cycles: Consequences for Puumala hantavirus epidemiology

2016 ◽  
Author(s):  
Dubois Adelaïde ◽  
Maxime Galan ◽  
Jean-François Cosson ◽  
Bertrand Gauffre ◽  
Heikki Henttonen ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Gene Flow ◽  
Bank Vole ◽  
Hemorrhagic Fever ◽  
Research Area ◽  
Density Fluctuations ◽  
Myodes Glareolus ◽  
Bank Voles ◽  
Active Research ◽  
Immune Related Genes

ABSTRACTUnderstanding how host dynamics, including variations of population size and dispersal, may affect the epidemiology of infectious diseases through ecological and evolutionary processes is an active research area. Here we focus on a bank vole (Myodes glareolus) metapopulation surveyed in Finland between 2005 and 2009. Bank vole is the reservoir of Puumala hantavirus (PUUV), the agent of nephropathia epidemica (NE, a mild form of hemorrhagic fever with renal symptom) in humans.M glareoluspopulations experience multiannual density fluctuations that may influence the level of genetic diversity maintained in bank voles, PUUV prevalence and NE occurrence. We examine bank vole metapopulation genetics at presumably neutral markers and immune-related genes involved in susceptibility to PUUV (Tnf-promoter,Mhc-Drb, Tlr4,Tlr7andMx2gene) to investigate the links between population dynamics, microevolutionary processes and PUUV epidemiology. We show that genetic drift slightly and transiently affects neutral and adaptive genetic variability within the metapopulation. Gene flow seems to counterbalance its effects during the multiannual density fluctuations. The low abundance phase may therefore be too short to impact genetic variation in the host, and consequently viral genetic diversity. Environmental heterogeneity does not seem to affect vole gene flow, which might explain the absence of spatial structure previously detected in PUUV in this area. Besides, our results suggest the role of vole dispersal on PUUV circulation through sex-specific and density-dependent movements. We find little evidence of selection acting on immune-related genes within this metapopulation. Footprint of positive selection is detected atTlr-4gene in 2008 only. We observe marginally significant associations betweenMhc-Drbhaplotypes and PUUV serology, and betweenMx2genotype and PUUV genogroups. These results show that microevolutionary changes and PUUV epidemiology in this metapopulation are mainly driven by neutral processes, although the relative effects of neutral and adaptive forces could vary temporally with density fluctuations.

scholarly journals Prevalence of the Puumala orthohantavirus Strains in the Pre-Kama Area of the Republic of Tatarstan, Russia

Pathogens ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 540 ◽  
Author(s):  
Yuriy Davidyuk ◽  
Anton Shamsutdinov ◽  
Emmanuel Kabwe ◽  
Ruzilya Ismagilova ◽  
Ekaterina Martynova ◽  
...  
Keyword(s):  
Hemorrhagic Fever ◽  
Federal District ◽  
European Part ◽  
Genome Segment ◽  
Genetic Lineage ◽  
Geographical Distance ◽  
Mild Form ◽  
Bank Voles ◽  
European Part Of Russia ◽  
The Republic

Puumala orthohantavirus (PUUV) causes nephropathia epidemica (NE), a mild form of hemorrhagic fever with renal syndrome (HFRS) commonly diagnosed in Europe. The majority of HFRS cases in the European part of Russia are diagnosed in the Volga Federal District, which includes the Republic of Tatarstan (RT). The current study aims to analyze the genetic variability of PUUV in Pre-Kama region of the RT bounded by the Volga, Kama, and Vyatka rivers. In 2017, bank voles were caught in seven isolated forest traps in the Pre-Kama region and for the 26 PUUV-positive samples, the partial small (S), medium (M), and large (L) genome segment sequences were obtained and analyzed. It was determined that all identified PUUV strains belong to the Russian (RUS) genetic lineage; however, the genetic distance between strains is not directly correlated with the geographical distance between bank vole populations. One of the identified strains has S and L segments produced from one parental strain, while the M segment was supplied by another, suggesting that this strain could be the reassortant. We suggest that the revealed pattern of the PUUV strains distribution could be the result of a series of successive multidirectional migratory flows of the bank voles to the Pre-Kama region in the postglacial period.

scholarly journals Cytokine Storm Combined with Humoral Immune Response Defect in Fatal Hemorrhagic Fever with Renal Syndrome Case, Tatarstan, Russia

Viruses ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 601 ◽  
Author(s):  
Ekaterina Garanina ◽  
Ekaterina Martynova ◽  
Yuriy Davidyuk ◽  
Emmanuel Kabwe ◽  
Konstantin Ivanov ◽  
...  
Keyword(s):  
Hemorrhagic Fever ◽  
Serum Levels ◽  
Human Case ◽  
Multiple Organ ◽  
Cytokine Storm ◽  
Humoral Immune ◽  
Cellular Immune Responses ◽  
Bank Voles ◽  
Cellular Immune ◽  
Necrosis Factor

Hemorrhagic fever with renal syndrome (HFRS) is endemic in Tatarstan, where thousands of cases are registered annually. Puumala orthohantavirus is commonly detected in human case samples as well as in captured bank voles, the rodent hosts. The pathogenesis of HFRS is still not well described, although the cytokine storm hypothesis is largely accepted. In this study, we present a comprehensive analysis of a fatal HFRS case compared with twenty four non-fatal cases where activation of the humoral and cellular immune responses, pro-inflammatory cytokines and disturbed blood coagulation were detected using immunological, histological, genetic and clinical approaches. Multiple organ failure combined with disseminated intravascular coagulation syndrome and acute renal failure was the cause of death. Decreased Interleukin (IL)-7 and increased IL-18, chemokine (C-C motif) ligand (CCL)-5, stem cell growth factor (SCGF)-b and tumor necrosis factor-beta (TNF-β) serum levels were found, supporting the cytokine storm hypothesis of hantavirus pathogenesis.

scholarly journals Bank vole immunoheterogeneity may limit Nephropatia Epidemica emergence in a French non-endemic region

Parasitology ◽  
2017 ◽  
Vol 145 (3) ◽  
pp. 393-407 ◽  
Author(s):  
A. DUBOIS ◽  
G. CASTEL ◽  
S. MURRI ◽  
C. PULIDO ◽  
J.-B. PONS ◽  
...  
Keyword(s):  
Bank Vole ◽  
Myodes Glareolus ◽  
Disease Emergence ◽  
Endemic Region ◽  
Natural Reservoir ◽  
Bank Voles ◽  
Free Region ◽  
Limited Dispersal ◽  
Antiviral Gene ◽  
French Region

SUMMARYEcoevolutionary processes affecting hosts, vectors and pathogens are important drivers of zoonotic disease emergence. In this study, we focused on nephropathia epidemica (NE), which is caused by Puumala hantavirus (PUUV) whose natural reservoir is the bank vole,Myodes glareolus. We questioned the possibility of NE emergence in a French region that is considered to be NE-free but that is adjacent to a NE-endemic region. We first confirmed the epidemiology of these two regions and we demonstrated the absence of spatial barriers that could have limited dispersal, and consequently, the spread of PUUV into the NE-free region. We next tested whether regional immunoheterogeneity could impact PUUV chances to circulate and persist in the NE-free region. We showed that bank voles from the NE-free region were sensitive to experimental PUUV infection. We observed high levels of immunoheterogeneity between individuals and also between regions. Antiviral gene expression (TnfandMx2) reached higher levels in bank voles from the NE-free region. During experimental infections, anti-PUUV antibody production was higher in bank voles from the NE-endemic region. These results indicated a lower susceptibility to PUUV for bank voles from this NE-free region, which might limit PUUV persistence and therefore, the risk of NE.

scholarly journals Infection Load and Prevalence of Novel Viruses Identified from the Bank Vole Do Not Associate with Exposure to Environmental Radioactivity

Viruses ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 44 ◽  
Author(s):  
Jenni Kesäniemi ◽  
Anton Lavrinienko ◽  
Eugene Tukalenko ◽  
Tapio Mappes ◽  
Phillip C. Watts ◽  
...  
Keyword(s):  
Bank Vole ◽  
Nuclear Power ◽  
Systemic Infection ◽  
Environmental Radioactivity ◽  
Myodes Glareolus ◽  
Environmental Radiation ◽  
Bank Voles ◽  
Zoonotic Viruses ◽  
Repair Activity ◽  
Radiation Contamination

Bank voles (Myodes glareolus) are host to many zoonotic viruses. As bank voles inhabiting areas contaminated by radionuclides show signs of immunosuppression, resistance to apoptosis, and elevated DNA repair activity, we predicted an association between virome composition and exposure to radionuclides. To test this hypothesis, we studied the bank vole virome in samples of plasma derived from animals inhabiting areas of Ukraine (contaminated areas surrounding the former nuclear power plant at Chernobyl, and uncontaminated areas close to Kyiv) that differed in level of environmental radiation contamination. We discovered four strains of hepacivirus and four new virus sequences: two adeno-associated viruses, an arterivirus, and a mosavirus. However, viral prevalence and viral load, and the ability to cause a systemic infection, was not dependent on the level of environmental radiation.

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