scholarly journals In Vivo Characterization of Tick-Borne Encephalitis Virus in Bank Voles (Myodes glareolus)

Viruses ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1069 ◽  
Author(s):  
Michelitsch ◽  
Tews ◽  
Klaus ◽  
Bestehorn-Willmann ◽  
Dobler ◽  
...  
Keyword(s):  
Bank Vole ◽  
Whole Blood ◽  
Clinical Signs ◽  
Encephalitis Virus ◽  
Myodes Glareolus ◽  
Bank Voles ◽  
Tick Borne Encephalitis ◽  
Tbev Strain ◽  
Tick Borne Encephalitis Virus

Tick-borne encephalitis is the most important tick-transmitted zoonotic virus infection in Eurasia, causing severe neurological symptoms in humans. The causative agent, the tick-borne encephalitis virus (TBEV), circulates between ticks and a variety of mammalian hosts. To study the interaction between TBEV and one of its suspected reservoir hosts, bank voles of the Western evolutionary lineage were inoculated subcutaneously with either one of eight TBEV strains or the related attenuated Langat virus, and were euthanized after 28 days. In addition, a subset of four strains was characterized in bank voles of the Carpathian linage. Six bank voles were inoculated per strain, and were housed together in groups of three with one uninfected in-contact animal each. Generally, most bank voles did not show any clinical signs over the course of infection. However, one infected bank vole died and three had to be euthanized prematurely, all of which had been inoculated with the identical TBEV strain (Battaune 17-H9, isolated in 2017 in Germany from a bank vole). All inoculated animals seroconverted, while none of the in-contact animals did. Viral RNA was detected via real-time RT-PCR in the whole blood samples of 31 out of 74 inoculated and surviving bank voles. The corresponding serum sample remained PCR-negative in nearly all cases (29/31). In addition, brain and/or spine samples tested positive in 11 cases, mostly correlating with a positive whole blood sample. Our findings suggest a good adaption of TBEV to bank voles, combining in most cases a low virulence phenotype with detectable virus replication and hinting at a reservoir host function of bank voles for TBEV.

scholarly journals The envelope protein of tick-borne encephalitis virus influences neuron entry, pathogenicity, and vaccine protection

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Richard Lindqvist ◽  
Ebba Rosendal ◽  
Elvira Weber ◽  
Naveed Asghar ◽  
Sarah Schreier ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Encephalitis Virus ◽  
Chimeric Virus ◽  
E Protein ◽  
Tick Borne Encephalitis ◽  
Neutralizing Capacity ◽  
Tbev Strain ◽  
Primary Mouse ◽  
Tick Borne Encephalitis Virus

Abstract Background Tick-borne encephalitis virus (TBEV) is considered to be the medically most important arthropod-borne virus in Europe. The symptoms of an infection range from subclinical to mild flu-like disease to lethal encephalitis. The exact determinants of disease severity are not known; however, the virulence of the strain as well as the immune status of the host are thought to be important factors for the outcome of the infection. Here we investigated virulence determinants in TBEV infection. Method Mice were infected with different TBEV strains, and high virulent and low virulent TBEV strains were chosen. Sequence alignment identified differences that were cloned to generate chimera virus. The infection rate of the parental and chimeric virus were evaluated in primary mouse neurons, astrocytes, mouse embryonic fibroblasts, and in vivo. Neutralizing capacity of serum from individuals vaccinated with the FSME-IMMUN® and Encepur® or combined were evaluated. Results We identified a highly pathogenic and neurovirulent TBEV strain, 93/783. Using sequence analysis, we identified the envelope (E) protein of 93/783 as a potential virulence determinant and cloned it into the less pathogenic TBEV strain Torö. We found that the chimeric virus specifically infected primary neurons more efficiently compared to wild-type (WT) Torö and this correlated with enhanced pathogenicity and higher levels of viral RNA in vivo. The E protein is also the major target of neutralizing antibodies; thus, genetic variation in the E protein could influence the efficiency of the two available vaccines, FSME-IMMUN® and Encepur®. As TBEV vaccine breakthroughs have occurred in Europe, we chose to compare neutralizing capacity from individuals vaccinated with the two different vaccines or a combination of them. Our data suggest that the different vaccines do not perform equally well against the two Swedish strains. Conclusions Our findings show that two amino acid substitutions of the E protein found in 93/783, A83T, and A463S enhanced Torö infection of neurons as well as pathogenesis and viral replication in vivo; furthermore, we found that genetic divergence from the vaccine strain resulted in lower neutralizing antibody titers in vaccinated individuals.

scholarly journals The Three Subtypes of Tick-Borne Encephalitis Virus Induce Encephalitis in a Natural Host, the Bank Vole (Myodes glareolus)

PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e81214 ◽  
Author(s):  
Elina Tonteri ◽  
Anja Kipar ◽  
Liina Voutilainen ◽  
Sirkka Vene ◽  
Antti Vaheri ◽  
...  
Keyword(s):  
Bank Vole ◽  
Natural Host ◽  
Encephalitis Virus ◽  
Myodes Glareolus ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus ◽  
Bank Vole Myodes Glareolus

scholarly journals First detection of tick-borne encephalitis virus in Ixodes ricinus ticks and their rodent hosts in Moscow, Russia

2018 ◽  
Author(s):  
Marat Makenov ◽  
Lyudmila Karan ◽  
Natalia Shashina ◽  
Marina Akhmetshina ◽  
Olga Zhurenkova ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Ixodes Ricinus ◽  
Small Mammals ◽  
Encephalitis Virus ◽  
Myodes Glareolus ◽  
Gps Tracking ◽  
Bank Voles ◽  
Tick Borne Encephalitis ◽  
Two Samples ◽  
Tick Borne Encephalitis Virus

AbstractHere, we report the first confirmed autochthonous tick-borne encephalitis case diagnosed in Moscow in 2016 and describe the detection of Tick-borne encephalitis virus (TBEV) in ticks and small mammals in a Moscow park.The paper includes data from two patients who were bitten by TBEV-infected ticks within the Moscow city limits; one of these cases led to the development of the meningeal form of TBE. Both TBEV-infected ticks attacked patients in the same area. We collected ticks and trapped small mammals in this area in 2017. All samples were screened for the presence of pathogens causing tick-borne diseases by PCR. The TBEV-positive ticks and small mammals’ tissue samples were subjected to virus isolation. The sequencing of the complete polyprotein gene of the positive samples was performed.A total of 227 questing ticks were collected. TBEV was detected in five specimens of Ixodes ricinus. We trapped 44 small mammals, mainly bank voles (Myodes glareolus) and pygmy field mice (Apodemus uralensis). Two samples of brain tissue from bank voles yielded a positive signal in RT-PCR for TBEV. We obtained six virus isolates from the ticks and brain tissue of a bank vole. Complete genome sequencing showed that the obtained isolates belong to the European subtype and have low diversity with sequence identities as high as 99.9%. GPS tracking showed that the maximum distance between the exact locations where the TBEV-positive ticks were collected was 185 m. We assume that the forest park was free of TBEV and that the virus was recently introduced.

Long-term presence of tick-borne encephalitis virus in experimentally infected bank voles (Myodes glareolus)

2021 ◽  
Vol 12 (4) ◽  
pp. 101693
Author(s):  
Anna Michelitsch ◽  
Christine Fast ◽  
Franziska Sick ◽  
Birke Andrea Tews ◽  
Karin Stiasny ◽  
...  
Keyword(s):  
Encephalitis Virus ◽  
Myodes Glareolus ◽  
Bank Voles ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus

scholarly journals The Envelope Protein of Tick-Borne Encephalitis Virus Influence Neuron Entry, Pathogenicity and Vaccine Protection

2020 ◽  
Author(s):  
Richard Lindqvist ◽  
Ebba Rosendal ◽  
Naveed Asghar ◽  
Sarah Schreier ◽  
Annasara Lenman ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Encephalitis Virus ◽  
Chimeric Virus ◽  
E Protein ◽  
Tick Borne Encephalitis ◽  
Neutralizing Capacity ◽  
Tbev Strain ◽  
Primary Mouse ◽  
Tick Borne Encephalitis Virus

Abstract Background: Tick-borne encephalitis virus (TBEV) is considered to be the medically most important arthropod-borne virus in Europe. The symptoms of an infection ranges from subclinical to mild flu-like disease to lethal encephalitis. The exact determinants of disease severity are not known, however, the virulence of the strain as well as the immune status of the host are thought to be important factors for the outcome of the infection. Here we investigated virulence determinants in TBEV infection.Method: Mice were infected with different TBEV strains, and high virulent and low virulent TBEV were chosen. Sequence alignment were used to identify differences that were cloned to generate chimera virus. The infection rate of the parental and chimeric virus were evaluated in primary mouse neurons, astrocytes and MEFs. Neutralizing capacity of serum from individuals vaccinated with the FSME-IMMUN® and Encepur® or combined were evaluated.Results: We identified a highly pathogenic and neurovirulent TBEV strain, 93/783. Using sequence analysis, we identified the envelope (E) protein of 93/783 as a potential virulence determinant and cloned it into the less pathogenic TBEV strain Torö. We found that the chimeric virus specifically infected primary neurons more efficiently compared to wild type (WT) Torö and this correlated with enhanced pathogenicity in vivo. The E protein is also the major target of neutralizing antibodies, thus genetic variation in the E protein could influence the efficiency of the two available vaccines, FSME-IMMUN® and Encepur®. As TBEV vaccine breakthroughs have occurred in Europe, we choose to compare neutralizing capacity from individuals vaccinated with the two different vaccines or a combination of them. Our data suggest that the different vaccines do not perform equally well against the two Swedish strains.Conclusions: Our findings show that two amino acid substitutions of the E protein found in 93/783, A83T and A463S, enhanced Torö infection of neurons as well as pathogenesis in vivo, furthermore we found that genetic divergence from the vaccine strain resulted in lower neutralizing antibody titers in vaccinated individuals.

TBE in Serbia

2021 ◽  
Author(s):  
Vladimir Petrović ◽  
Elizabeta Ristanović ◽  
Aleksandar Potkonjak
Keyword(s):  
Clinical Signs ◽  
Encephalitis Virus ◽  
Former Yugoslavia ◽  
Serological Testing ◽  
Tick Borne Encephalitis ◽  
The Republic ◽  
Tick Borne Encephalitis Virus

Tick-borne encephalitis virus (TBEV) was first isolated in the former Yugoslavia in 1953 from the blood of infected human patients in Slovenia.1 The virus was isolated from ticks in 1954, also in Slovenia.2 Thereafter a number of tick-borne encephalitis (TBE) foci were registered in the western part of the country, while in the Republic of Serbia such foci were not registered. In the period following 1969, no new infections with TBEV could be confirmed in the Republic of Serbia through the routine serological testing of samples from more than 1,000 patients with clinical signs of meningitis and encephalitis, as conducted in laboratories of the Institute of Immunobiology and Virology “Torlak” in Belgrade.3

scholarly journals Tick-Borne Encephalitis Virus: Seasonal and Annual Variation of Epidemiological Parameters Related to Nymph-to-Larva Transmission and Exposure of Small Mammals

Pathogens ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 518
Author(s):  
Laure Bournez ◽  
Gerald Umhang ◽  
Marie Moinet ◽  
Céline Richomme ◽  
Jean-Michel Demerson ◽  
...  
Keyword(s):  
Small Mammals ◽  
Temporal Variations ◽  
Encephalitis Virus ◽  
Myodes Glareolus ◽  
Mountain Forest ◽  
Annual Variations ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus ◽  
Over Time ◽  
Epidemiological Parameters

A greater knowledge of the ecology of the natural foci of tick-borne encephalitis virus (TBEV) is essential to better assess the temporal variations of the risk of tick-borne encephalitis for humans. To describe the seasonal and inter-annual variations of the TBEV-cycle and the epidemiological parameters related to TBEV nymph-to-larva transmission, exposure of small mammals to TBEV, and tick aggregation on small mammals, a longitudinal survey in ticks and small mammals was conducted over a 3-year period in a mountain forest in Alsace, eastern France. TBEV prevalence in questing nymphs was lower in 2013 than in 2012 and 2014, probably because small mammals (Myodes glareolus and Apodemus flavicollis) were more abundant in 2012, which reduced tick aggregation and co-feeding transmission between ticks. The prevalence of TBEV in questing nymphs was higher in autumn than spring. Despite these variations in prevalence, the density of infected questing nymphs was constant over time, leading to a constant risk for humans. The seroprevalence of small mammals was also constant over time, although the proportion of rodents infested with ticks varied between years and seasons. Our results draw attention to the importance of considering the complex relationship between small mammal densities, tick aggregation on small mammals, density of infected questing nymphs, and prevalence of infected nymphs in order to forecast the risk of TBEV for humans.

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 Spectrum of antiviral activity of 4-aminopyrimidine N-oxides against a broad panel of tick-borne encephalitis virus strains

2020 ◽  
Vol 28 ◽  
pp. 204020662094346
Author(s):  
Evgenia V Dueva ◽  
Ksenia K Tuchynskaya ◽  
Liubov I Kozlovskaya ◽  
Dmitry I Osolodkin ◽  
Kseniya N Sedenkova ◽  
...  
Keyword(s):  
Encephalitis Virus ◽  
Northern Eurasia ◽  
Virus Particles ◽  
E Protein ◽  
Tick Borne Encephalitis ◽  
Tbev Strain ◽  
Amino Phenol ◽  
Tick Borne Encephalitis Virus ◽  
Immature Virus

Tick-borne encephalitis is an important human arbovirus neuroinfection spread across the Northern Eurasia. Inhibitors of tick-borne encephalitis virus (TBEV) strain Absettarov, presumably targeting E protein n-octyl-β-d-glucoside (β-OG) pocket, were reported earlier. In this work, these inhibitors were tested in vitro against seven strains representing three main TBEV subtypes. The most potent compound, 2-[(2-methyl-1-oxido-5,6,7,8-tetrahydroquinazolin-4-yl)amino]-phenol, showed EC50 values lower than 22 µM against all the tested strains. Nevertheless, EC50 values for virus samples of certain strains demonstrated a substantial variation, which appeared to be consistent with the presence of E protein not only in infectious virions, but also in non-infectious and immature virus particles, protein aggregates, and membrane complexes.

scholarly journals Adaptation of Tick-Borne Encephalitis Virus to BHK-21 Cells Results in the Formation of Multiple Heparan Sulfate Binding Sites in the Envelope Protein and Attenuation In Vivo

2001 ◽  
Vol 75 (12) ◽  
pp. 5627-5637 ◽  
Author(s):  
Christian W. Mandl ◽  
Helga Kroschewski ◽  
Steven L. Allison ◽  
Regina Kofler ◽  
Heidemarie Holzmann ◽  
...  
Keyword(s):  
Heparan Sulfate ◽  
Encephalitis Virus ◽  
Surface Glycoprotein ◽  
Glycoprotein E ◽  
Recombinant Viruses ◽  
Adult Mice ◽  
Tick Borne Encephalitis ◽  
Significant Attenuation ◽  
Tick Borne Encephalitis Virus

ABSTRACT Propagation of the flavivirus tick-borne encephalitis virus in BHK-21 cells selected for mutations within the large surface glycoprotein E that increased the net positive charge of the protein. In the course of 16 independent experiments, 12 different protein E mutation patterns were identified. These were located in all three of the structural domains and distributed over almost the entire upper and lateral surface of protein E. The mutations resulted in the formation of local patches of predominantly positive surface charge. Recombinant viruses carrying some of these mutations in a defined genetic backbone showed heparan sulfate (HS)-dependent phenotypes, resulting in an increased specific infectivity and binding affinity for BHK-21 cells, small plaque formation in porcine kidney cells, and significant attenuation of neuroinvasiveness in adult mice. Our results corroborate the notion that the selection of attenuated HS binding mutants is a common and frequent phenomenon during the propagation of viruses in cell culture and suggest a major role for HS dependence in flavivirus attenuation. Recognition of this principle may be of practical value for designing attenuated flavivirus strains in the future.

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