Borrelia afzelii does not suppress the development of anti-tick immunity in bank voles

AbstractVector-borne pathogens manipulate their vertebrate hosts to enhance their transmission to arthropod vectors. The ability of vertebrate hosts to develop acquired immunity against arthropod vectors represents an existential threat for both the vector and the pathogen. The purpose of the study was to test whether the tick-borne spirochete bacterium Borrelia afzelii could suppress the development of acquired immunity to its tick vector Ixodes ricinus in the bank vole Myodes glareolus, which is an important host for both the tick and the pathogen. We created a group of B. afzelii-infected bank voles and an uninfected control group by exposing lab-reared animals to infected or uninfected ticks. At 1, 2, and 3 months post-infection, all bank voles were infested with larval I. ricinus ticks. The bank voles developed a strong antibody response against tick salivary gland extract proteins. This anti-tick immunity had negative effects on tick fitness traits including engorged larval weight, unfed nymphal weight, larva-to-nymph molting time and larva-to-nymph molting success. Infection with B. afzelii did not suppress the development of acquired immunity against I. ricinus ticks. The development of anti-tick immunity was strongly correlated with a dramatic temporal decline in both the bacterial abundance in the host ear tissues and the host-tick transmission success of B. afzelii. Our study suggests that the development of anti-tick immunity in bank voles has important consequences for the density of infected ticks and the risk of Lyme borreliosis.ImportanceMany pathogens enhance their persistence and transmission by suppressing the immune system of their host. We used an experimental infection approach to test whether the Lyme disease pathogen, Borrelia afzelii, could suppress the development of acquired immunity against its tick vector (Ixodes ricinus) in the bank vole (Myodes glareolus), but found no evidence for this phenomenon. Uninfected and B. afzelii-infected bank voles both developed a strong IgG antibody response against tick salivary gland extract following repeated infestations with I. ricinus ticks. The development of anti-tick immunity was negatively correlated with the abundance of B. afzelii in ear tissue biopsies and with host-to-tick transmission to I. ricinus ticks. Our study suggests that anti-tick immunity in the bank vole reduces the prevalence of this important tick-borne pathogen.

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Infection Dynamics of the Tick-Borne Pathogen “Candidatus Neoehrlichia mikurensis” and Coinfections with Borrelia afzelii in Bank Voles in Southern Sweden

Applied and Environmental Microbiology ◽

10.1128/aem.03469-13 ◽

2013 ◽

Vol 80 (5) ◽

pp. 1645-1649 ◽

Cited By ~ 14

Author(s):

Martin Andersson ◽

Kristin Scherman ◽

Lars Råberg

Keyword(s):

Myodes Glareolus ◽

Content Type ◽

Borrelia Afzelii ◽

Bank Voles ◽

Infection Dynamics ◽

Vertebrate Hosts ◽

High Level ◽

Longitudinal Sampling ◽

Neoehrlichia Mikurensis ◽

Sampling Season

ABSTRACTThe tick-borne bacterium “CandidatusNeoehrlichia mikurensis” has recently been recognized as a human pathogen. Together withBorrelia afzelii, it is one of the most common pathogens found in the tickIxodes ricinus. Here, we compared the epidemiologies of “Ca. Neoehrlichia mikurensis” andB. afzeliiby longitudinal sampling from May to September in one of their most abundant vertebrate hosts, the bank vole (Myodes glareolus), using real-time PCR for detection and quantification. The prevalences of “Ca. Neoehrlichia mikurensis” andB. afzeliiwere determined to be 19% (50/261) and 22% (56/261), respectively. The prevalence of “Ca. Neoehrlichia mikurensis” increased significantly during the sampling season. The clearance rate of “Ca. Neoehrlichia mikurensis” was significantly higher than that ofB. afzelii. We found a high frequency of double infections; 46% of all samples infected with “Ca. Neoehrlichia mikurensis” also had a coinfection withB. afzelii. The frequency of coinfections was significantly higher than expected from the prevalence of each pathogen. The high level of coinfections can be caused by interactions between the pathogens or might reflect variation in general susceptibility among voles.

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Polymorphism of TLR2 in bank vole populations in North Eastern Poland is not associated with Borrelia afzelii infection prevalence

Mammal Research ◽

10.1007/s13364-020-00518-7 ◽

2020 ◽

Vol 65 (4) ◽

pp. 779-791

Author(s):

Ewa Tarnowska ◽

Magdalena Niedziałkowska ◽

Joanna Stojak ◽

Bogumiła Jędrzejewska

Keyword(s):

Bank Vole ◽

Innate Immune ◽

Myodes Glareolus ◽

Infection Prevalence ◽

Borrelia Afzelii ◽

Immune Genes ◽

Ne Poland ◽

Bank Voles ◽

North Eastern ◽

Innate Immune Genes

Abstract Polymorphism in innate immune genes in host populations can structure spatial variation in the prevalence of infectious diseases. In Europe, Borrelia afzelii is an important tick-borne pathogen of small mammals including the bank voles (Myodes glareolus). The Toll-like receptor 2 (TLR2) is an innate immune receptor that is important for detecting Borrelia burgdorferi sensu lato pathogens. The TLR2 gene is polymorphic in bank vole populations and is classified into four distinct clusters: C1, C2, C3, and C4. The C2 and C4 clusters versus the C1 and C3 clusters are associated with lower versus higher infection prevalence, respectively. We detected three TLR2 clusters in 487 bank voles from 30 populations in NE Poland: 84.2% of the obtained sequences belonged to the C1 variant, 7.2% to C2, and 8.6% to C3. However, no clear spatial structure of TLR2 clusters among the populations was detected. B. afzelii infection prevalence across all studied individuals was 12.1% and varied from 0 to 37.5% among populations. There were no significant differences in B. afzelii prevalence among voles carrying alleles of different TLR2 clusters, or between individuals belonging to two mtDNA lineages. Most infected individuals were adults, and males were infected more often than females. There was no significant relationship between the prevalence of TLR2 clusters in the vole populations and climatic and environmental factors within the study area. We therefore could not confirm an adaptive role of the TLR2 C2 alleles in reducing B. afzelii infection prevalence in bank voles.

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

Parasitology ◽

10.1017/s0031182017001548 ◽

2017 ◽

Vol 145 (3) ◽

pp. 393-407 ◽

Cited By ~ 6

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.

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

Viruses ◽

10.3390/v12010044 ◽

2019 ◽

Vol 12 (1) ◽

pp. 44 ◽

Cited By ~ 1

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

Viruses ◽

10.3390/v12020237 ◽

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.

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

Open Biology ◽

10.1098/rsob.170135 ◽

2017 ◽

Vol 7 (9) ◽

pp. 170135 ◽

Cited By ~ 4

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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Accumulation of point mutations and reassortment of genomic RNA segments are involved in the microevolution of Puumala hantavirus in a bank vole (Myodes glareolus) population

Journal of General Virology ◽

10.1099/vir.0.2008/001248-0 ◽

2008 ◽

Vol 89 (7) ◽

pp. 1649-1660 ◽

Cited By ~ 41

Author(s):

Maria Razzauti ◽

Angelina Plyusnina ◽

Heikki Henttonen ◽

Alexander Plyusnin

Keyword(s):

Genetic Diversity ◽

Bank Vole ◽

Local Population ◽

Point Mutations ◽

Myodes Glareolus ◽

Stabilizing Selection ◽

Genetic Lineage ◽

Nucleotide Substitutions ◽

Bank Voles ◽

L Segment

The genetic diversity of Puumala hantavirus (PUUV) was studied in a local population of its natural host, the bank vole (Myodes glareolus). The trapping area (2.5×2.5 km) at Konnevesi, Central Finland, included 14 trapping sites, at least 500 m apart; altogether, 147 voles were captured during May and October 2005. Partial sequences of the S, M and L viral genome segments were recovered from 40 animals. Seven, 12 and 17 variants were detected for the S, M and L sequences, respectively; these represent new wild-type PUUV strains that belong to the Finnish genetic lineage. The genetic diversity of PUUV strains from Konnevesi was 0.2–4.9 % for the S segment, 0.2–4.8 % for the M segment and 0.2–9.7 % for the L segment. Most nucleotide substitutions were synonymous and most deduced amino acid substitutions were conservative, probably due to strong stabilizing selection operating at the protein level. Based on both sequence markers and phylogenetic clustering, the S, M and L sequences could be assigned to two groups, ‘A’ and ‘B’. Notably, not all bank voles carried S, M and L sequences belonging to the same group, i.e. SAMALA or SBMBLB. A substantial proportion (8/40, 20 %) of the newly characterized PUUV strains possessed reassortant genomes such as SBMALA, SAMBLB or SBMALB. These results suggest that at least some of the PUUV reassortants are viable and can survive in the presence of their parental strains.

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

Epidemiology and Infection ◽

10.1017/s0950268816002557 ◽

2016 ◽

Vol 145 (3) ◽

pp. 434-439 ◽

Cited By ~ 1

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.

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First isolation and genetic characterization of Puumala orthohantavirus strains from France

10.1101/2020.08.27.270181 ◽

2020 ◽

Cited By ~ 2

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.

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

10.1101/048082 ◽

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.

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