scholarly journals A novel experimental system reveals immunoregulatory responses as mediators of persistent orthohantavirus infections in a rodent reservoir host

2019 ◽  
Author(s):  
Tomas Strandin ◽  
Teemu Smura ◽  
Paula Ahola ◽  
Kirsi Aaltonen ◽  
Tarja Sironen ◽  
...  
Keyword(s):  
Immune Responses ◽  
Virus Replication ◽  
Bank Vole ◽  
Experimental System ◽  
Reservoir Host ◽  
Myodes Glareolus ◽  
Bank Voles ◽  
Human Infections ◽  
Reservoir Hosts

AbstractOrthohantaviruses are globally emerging zoonotic pathogens. Human infections are characterized by an overt immune response that is efficient at counteracting virus replication but can also cause severe tissue damage. In contrast, orthohantavirus infections in rodent reservoir hosts are persistent and asymptomatic. The mechanisms facilitating asymptomatic virus persistence in reservoir hosts are not well understood but could help to guide therapeutic strategies for human infections. Here we report on a study using in vivo and in vitro experiments to investigate immune responses associated with persistent Puumala orthohantavirus (PUUV) infections in the bank vole (Myodes glareolus), its reservoir host. We examined adaptive cellular and humoral responses by quantifying changes in T-cell related gene expression in the spleen and immunoglobulin (Ig) responses in blood, respectively. Since existing Vero E6-cell adapted hantavirus isolates have been demonstrated to have lost their wild-type infection characteristics, infections were conducted with a novel PUUV strain isolated on a bank vole cell line. Whole virus genome sequencing revealed that only minor sequence changes occurred during the isolation process, and critically, experimental infections of bank voles with the new isolate resembled natural infections. In vitro infection of bank vole splenocytes with the novel isolate demonstrated that PUUV promotes immunoregulatory responses by inducing interleukin-10, a cytokine strongly associated with chronic viral infections. A delayed virus-specific humoral response occurred in experimentally infected bank voles, which is likely to allow for initial virus replication and the establishment of persistent infections. These results suggest that host immunoregulation facilitates persistent orthohantavirus infections in reservoir hosts.ImportanceOrthohantaviruses are a group of global pathogens that regularly spillover from rodent reservoirs into humans and can cause severe disease. Conversely, infections in reservoir hosts do not cause obvious adverse effects. The mechanisms responsible for persistent asymptomatic reservoir infections are unknown, and progress has been hindered by the absence of an adequate experimental system. Knowledge on these mechanisms could help provide strategies to treat human infections. We developed and validated an experimental system based on an orthohantavirus isolated in cells of its vole reservoir host. Using animal and cell culture experiments in the reservoir host system, we demonstrated that infection suppresses immunity in the vole reservoir via specific mechanisms, likely allowing the virus to take hold and preventing immune responses that can cause self-damage.

scholarly journals In Vivo Characterization of a Bank Vole-Derived Cowpox Virus Isolate in Natural Hosts and the Rat Model

Viruses ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 237
Author(s):  
Saskia Weber ◽  
Kathrin Jeske ◽  
Rainer G. Ulrich ◽  
Christian Imholt ◽  
Jens Jacob ◽  
...  
Keyword(s):  
Bank Vole ◽  
Wistar Rats ◽  
Reservoir Host ◽  
Myodes Glareolus ◽  
Replication Capacity ◽  
Cowpox Virus ◽  
Saguinus Oedipus ◽  
Bank Voles ◽  
Common Voles

Cowpox virus (CPXV) belongs to the genus Orthopoxvirus in the Poxviridae family and is endemic in western Eurasia. Based on seroprevalence studies in different voles from continental Europe and UK, voles are suspected to be the major reservoir host. Recently, a CPXV was isolated from a bank vole (Myodes glareolus) in Germany that showed a high genetic similarity to another isolate originating from a Cotton-top tamarin (Saguinus oedipus). Here we characterize this first bank vole-derived CPXV isolate in comparison to the related tamarin-derived isolate. Both isolates grouped genetically within the provisionally called CPXV-like 3 clade. Previous phylogenetic analysis indicated that CPXV is polyphyletic and CPXV-like 3 clade represents probably a different species if categorized by the rules used for other orthopoxviruses. Experimental infection studies with bank voles, common voles (Microtus arvalis) and Wistar rats showed very clear differences. The bank vole isolate was avirulent in both common voles and Wistar rats with seroconversion seen only in the rats. In contrast, inoculated bank voles exhibited viral shedding and seroconversion for both tested CPXV isolates. In addition, bank voles infected with the tamarin-derived isolate experienced a marked weight loss. Our findings allow for the conclusion that CPXV isolates might differ in their replication capacity in different vole species and rats depending on their original host. Moreover, the results indicate host-specific differences concerning CPXV-specific virulence. Further experiments are needed to identify individual virulence and host factors involved in the susceptibility and outcome of CPXV-infections in the different reservoir hosts.

scholarly journals Validation of the Puumala virus rapid field test for bank voles in Germany

2016 ◽  
Vol 145 (3) ◽  
pp. 434-439 ◽  
Author(s):  
D. REIL ◽  
C. IMHOLT ◽  
U. M. ROSENFELD ◽  
S. DREWES ◽  
S. FISCHER ◽  
...  
Keyword(s):  
Field Test ◽  
Bank Vole ◽  
Myodes Glareolus ◽  
Puumala Virus ◽  
Short Term ◽  
Bank Voles ◽  
Moderate Disease ◽  
Comparison Of The Results ◽  
Human Infections ◽  
Puuv Strain

SUMMARYPuumala virus (PUUV) causes many human infections in large parts of Europe and can lead to mild to moderate disease. The bank vole (Myodes glareolus) is the only reservoir of PUUV in Central Europe. A commercial PUUV rapid field test for rodents was validated for bank-vole blood samples collected in two PUUV-endemic regions in Germany (North Rhine-Westphalia and Baden-Württemberg). A comparison of the results of the rapid field test and standard ELISAs indicated a test efficacy of 93–95%, largely independent of the origin of the antigens used in the ELISA. In ELISAs, reactivity for the German PUUV strain was higher compared to the Swedish strain but not compared to the Finnish strain, which was used for the rapid field test. In conclusion, the use of the rapid field test can facilitate short-term estimation of PUUV seroprevalence in bank-vole populations in Germany and can aid in assessing human PUUV infection risk.

scholarly journals Molecular Detection and Characterization of the First Cowpox Virus Isolate Derived from a Bank Vole

Viruses ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1075 ◽  
Author(s):  
Kathrin Jeske ◽  
Saskia Weber ◽  
Florian Pfaff ◽  
Christian Imholt ◽  
Jens Jacob ◽  
...  
Keyword(s):  
Bank Vole ◽  
Large Scale ◽  
Reservoir Host ◽  
Myodes Glareolus ◽  
Phenotypic Characterization ◽  
Cowpox Virus ◽  
Bank Voles ◽  
Wide Range ◽  
Common Voles

Cowpox virus (CPXV) is a zoonotic orthopoxvirus (OPV) that infects a wide range of mammals. CPXV-specific DNA and antibodies were detected in different vole species, such as common voles (Microtus arvalis) and bank voles (Myodes glareolus). Therefore, voles are the putative main reservoir host of CPXV. However, CPXV was up to now only isolated from common voles. Here we report the detection and isolation of a bank vole-derived CPXV strain (GerMygEK 938/17) resulting from a large-scale screening of bank voles collected in Thuringia, Germany, during 2017 and 2018. Phylogenetic analysis using the complete viral genome sequence indicated a high similarity of the novel strain to CPXV clade 3 and to OPV “Abatino” but also to Ectromelia virus (ECTV) strains. Phenotypic characterization of CPXV GerMygEK 938/17 using inoculation of embryonated chicken eggs displayed hemorrhagic pock lesions on the chorioallantoic membrane that are typical for CPXV but not for ECTV. CPXV GerMygEK 938/17 replicated in vole-derived kidney cell lines but at lower level than on Vero76 cell line. In conclusion, the first bank vole-derived CPXV isolate provides new insights into the genetic variability of CPXV in the putative reservoir host and is a valuable tool for further studies about CPXV-host interaction and molecular evolution of OPV.

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.

scholarly journals Evolution of Nipah Virus Infection: Past, Present, and Future Considerations

2021 ◽  
Vol 6 (1) ◽  
pp. 24
Author(s):  
Naomi Hauser ◽  
Alexis C. Gushiken ◽  
Shivakumar Narayanan ◽  
Shyam Kottilil ◽  
Joel V. Chua
Keyword(s):  
Case Fatality Rate ◽  
Nipah Virus ◽  
Case Fatality ◽  
Therapeutic Agents ◽  
Reservoir Host ◽  
Fruit Bats ◽  
Intermediate Hosts ◽  
Mode Of Transmission ◽  
Human Infections ◽  
Reservoir Hosts

Nipah virus (NiV) is a zoonotic paramyxovirus of the Henipavirus genus first identified in Malaysia in 1998. Henipaviruses have bat reservoir hosts and have been isolated from fruit bats found across Oceania, Asia, and Africa. Bat-to-human transmission is thought to be the primary mode of human NiV infection, although multiple intermediate hosts are described. Human infections with NiV were originally described as a syndrome of fever and rapid neurological decline following contact with swine. More recent outbreaks describe a syndrome with prominent respiratory symptoms and human-to-human transmission. Nearly annual outbreaks have been described since 1998 with case fatality rates reaching greater than 90%. The ubiquitous nature of the reservoir host, increasing deforestation, multiple mode of transmission, high case fatality rate, and lack of effective therapy or vaccines make NiV’s pandemic potential increasingly significant. Here we review the epidemiology and microbiology of NiV as well as the therapeutic agents and vaccines in development.

scholarly journals Population genomics of bank vole populations reveals associations between immune related genes and the epidemiology of Puumala hantavirus in Sweden

2017 ◽  
Author(s):  
Audrey Rohfritsch ◽  
Maxime Galan ◽  
Mathieu Gautier ◽  
Karim Gharbi ◽  
Gert Olsson ◽  
...  
Keyword(s):  
High Throughput ◽  
Bank Vole ◽  
High Throughput Sequencing ◽  
Population Genomics ◽  
Reservoir Host ◽  
Model Organisms ◽  
Myodes Glareolus ◽  
A Genome ◽  
Outlier Loci ◽  
Immune Related Genes

AbstractInfectious pathogens are major selective forces acting on individuals. The recent advent of high-throughput sequencing technologies now enables to investigate the genetic bases of resistance/susceptibility to infections in non-model organisms. From an evolutionary perspective, the analysis of the genetic diversity observed at these genes in natural populations provides insight into the mechanisms maintaining polymorphism and their epidemiological consequences. We explored these questions in the context of the interactions between Puumala hantavirus (PUUV) and its reservoir host, the bank vole Myodes glareolus. Despite the continuous spatial distribution of M. glareolus in Europe, PUUV distribution is strongly heterogeneous. Different defence strategies might have evolved in bank voles as a result of co-adaptation with PUUV, which may in turn reinforce spatial heterogeneity in PUUV distribution. We performed a genome scan study of six bank vole populations sampled along a North/South transect in Sweden, including PUUV endemic and non-endemic areas. We combined candidate gene analyses (Tlr4, Tlr7, Mx2 genes) and high throughput sequencing of RAD (Restriction-site Associated DNA) markers. We found evidence for outlier loci showing high levels of genetic differentiation. Ten outliers among the 52 that matched to mouse protein-coding genes corresponded to immune related genes and were detected using ecological associations with variations in PUUV prevalence. One third of the enriched pathways concerned immune processes, including platelet activation and TLR pathway. In the future, functional experimentations should enable to confirm the role of these these immune related genes with regard to the interactions between M. glareolus and PUUV.

scholarly journals High-resolution melting analysis identifies reservoir hosts of zoonotic Leishmania parasites in Tunisia

2022 ◽  
Vol 15 (1) ◽  
Author(s):  
Moufida Derghal ◽  
Abir Tebai ◽  
Ghofrane Balti ◽  
Hajer Souguir-Omrani ◽  
Jomaa Chemkhi ◽  
...  
Keyword(s):  
High Resolution ◽  
Leishmania Major ◽  
High Resolution Melting ◽  
Reservoir Host ◽  
Sand Fly ◽  
Canine Leishmaniasis ◽  
Multiple Infections ◽  
Epidemiological Surveys ◽  
Reservoir Hosts

Abstract Background Leishmaniasis is endemic in Tunisia and presents with different clinical forms, caused by the species Leishmania infantum, Leishmania major, and Leishmania tropica. The life cycle of Leishmania is complex and involves several phlebotomine sand fly vectors and mammalian reservoir hosts. The aim of this work is the development and evaluation of a high-resolution melting PCR (PCR-HRM) tool to detect and identify Leishmania parasites in wild and domestic hosts, constituting confirmed (dogs and Meriones rodents) or potential (hedgehogs) reservoirs in Tunisia. Methods Using in vitro-cultured Leishmania isolates, PCR-HRM reactions were developed targeting the 7SL RNA and HSP70 genes. Animals were captured or sampled in El Kef Governorate, North West Tunisia. DNA was extracted from the liver, spleen, kidney, and heart from hedgehogs (Atelerix algirus) (n = 3) and rodents (Meriones shawi) (n = 7) and from whole blood of dogs (n = 12) that did not present any symptoms of canine leishmaniasis. In total, 52 DNA samples were processed by PCR-HRM using both pairs of primers. Results The results showed melting curves enabling discrimination of the three Leishmania species present in Tunisia, and were further confirmed by Sanger sequencing. Application of PCR-HRM assays on reservoir host samples showed that overall among the examined samples, 45 were positive, while seven were negative, with no Leishmania infection. Meriones shawi were found infected with L. major, while dogs were infected with L. infantum. However, co-infections with L. major/L. infantum species were detected in four Meriones specimens and in all tested hedgehogs. In addition, multiple infections with the three Leishmania species were found in one hedgehog specimen. Sequence analyses of PCR-HRM products corroborated the Leishmania species found in analyzed samples. Conclusions The results of PCR-HRM assays applied to field specimens further support the possibility of hedgehogs as reservoir hosts of Leishmania. In addition, we showed their usefulness in the diagnosis of canine leishmaniasis, specifically in asymptomatic dogs, which will ensure a better evaluation of infection extent, thus improving elaboration of control programs. This PCR-HRM method is a robust and reliable tool for molecular detection and identification of Leishmania and can be easily implemented in epidemiological surveys in endemic regions. Graphical Abstract

Environmental and ecological potential for enzootic cycles of Puumala hantavirus in Great Britain

2009 ◽  
Vol 138 (1) ◽  
pp. 91-98 ◽  
Author(s):  
E. BENNETT ◽  
J. CLEMENT ◽  
P. SANSOM ◽  
I. HALL ◽  
S. LEACH ◽  
...  
Keyword(s):  
Great Britain ◽  
Environmental Factors ◽  
Bank Vole ◽  
Regression Models ◽  
Reservoir Host ◽  
Myodes Glareolus ◽  
Puumala Virus ◽  
Climate Data ◽  
Northwest Europe ◽  
Climatic Constraints

SUMMARYPuumala virus (PUUV) is a zoonotic rodent-borne hantavirus in continental Europe. Its reservoir host, the bank vole (Myodes glareolus), is ubiquitous in Great Britain (GB); however, there has been no reported incidence of virus in either animals or humans. In northwest Europe, increases in bank vole numbers, stimulated by increases in production of beech/oak crops (mast), are associated with outbreaks of nephropathia epidemica (NE) in humans. These so-called ‘mast years’ are determined by sequential climatic events. This paper investigates the contribution of a number of ecological and environmental factors driving outbreaks of PUUV in northwest Europe and assesses whether such factors might also permit enzootic PUUV circulation in GB. Analysis of GB climate data, using regression models, confirms that mast years in GB are stimulated, and can be predicted, by the same climatic events as mast years in PUUV-endemic regions of northwest Europe. A number of other possible non-climatic constraints on enzootic cycles are discussed.

scholarly journals Glareosin: a novel sexually dimorphic urinary lipocalin in the bank vole, Myodes glareolus

Open Biology ◽  
2017 ◽  
Vol 7 (9) ◽  
pp. 170135 ◽  
Author(s):  
Grace M. Loxley ◽  
Jennifer Unsworth ◽  
Michael J. Turton ◽  
Alexandra Jebb ◽  
Kathryn S. Lilley ◽  
...  
Keyword(s):  
Bank Vole ◽  
Disulfide Bonds ◽  
Scent Marking ◽  
Myodes Glareolus ◽  
Sexually Dimorphic ◽  
Odorant Binding Proteins ◽  
Bank Voles ◽  
Odorant Binding ◽  
Bank Vole Myodes Glareolus ◽  
Novel Protein

The urine of bank voles ( Myodes glareolus ) contains substantial quantities of a small protein that is expressed at much higher levels in males than females, and at higher levels in males in the breeding season. This protein was purified and completely sequenced at the protein level by mass spectrometry. Leucine/isoleucine ambiguity was completely resolved by metabolic labelling, monitoring the incorporation of dietary deuterated leucine into specific sites in the protein. The predicted mass of the sequenced protein was exactly consonant with the mass of the protein measured in bank vole urine samples, correcting for the formation of two disulfide bonds. The sequence of the protein revealed that it was a lipocalin related to aphrodisin and other odorant-binding proteins (OBPs), but differed from all OBPs previously described. The pattern of secretion in urine used for scent marking by male bank voles, and the similarity to other lipocalins used as chemical signals in rodents, suggest that this protein plays a role in male sexual and/or competitive communication. We propose the name glareosin for this novel protein to reflect the origin of the protein and to emphasize the distinction from known OBPs.

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