Comparative analysis of European bat lyssavirus 1 pathogenicity in the mouse model
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PROVIDER: PRJEB20390 | ENA |
REPOSITORIES: ENA
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Project description:Background: Coevolution between pathogens and their hosts decreases host morbidity and mortality. Bats can tolerate viruses which can be lethal to other vertebrate orders, including humans. Bat adaptations to infection include localized immune response, early pathogen sensing, high interferon expression without pathogen stimulation, and regulated inflammatory response. The immune reaction is costly, and bats suppress high-cost metabolism during torpor. In the temperate zone, bats hibernate in winter, utilizing a specific behavioural adaptation to survive detrimental environmental conditions and lack of energy resources. Hibernation torpor involves major physiological changes that pose an additional challenge to bat-pathogen coexistence. Here, we compared bat cellular reaction to viral challenge under conditions simulating hibernation, evaluating the changes between torpor and euthermia. Results: We infected the olfactory nerve-derived cell culture of Myotis myotis with an endemic bat pathogen, European bat lyssavirus 1 (EBLV-1). After infection, the bat cells were cultivated at two different temperatures – 37 ◦ C and 5 ◦ C - to examine the cell response during conditions simulating euthermia and torpor, respectively. The mRNA isolated from the cells was sequenced and analysed for differential gene expression attributable to the temperature and/or infection treatment. In conditions simulating euthermia, infected bat cells produce an excess signalling by multitude of pathways involved in apoptosis and immune regulation influencing proliferation of regulatory cell types which can, in synergy with other produced cytokines, contribute to viral tolerance. We found no up- or downregulated genes expressed in infected cells cultivated at conditions simulating torpor compared to non-infected cells cultivated under the same conditions. When studying the reaction of uninfected cells to the temperature treatment, bat cells show an increased production of heat shock proteins (HSPs) with chaperone activity, improving the bat’s ability to repair molecular structures damaged due to the stress related to the temperature change. Conclusions: The lack of bat cell reaction to infection in conditions simulating hibernation may contribute to the virus tolerance or persistence in bats. Together with the cell damage repair mechanisms induced in response to hibernation, the immune regulation may promote bats’ ability to act as reservoirs of zoonotic viruses such as lyssaviruses.
2023-03-29 | GSE228404 | GEO
Project description:European bat lyssavirus 1 is responsible for most bat rabies cases in Europe. Although EBLV-1 isolates display a high degree of sequence identity, different sublineages exist. In individual isolates various insertions and deletions have been identified, with unknown impact on viral replication and pathogenicity. In order to assess whether different genetic features of EBLV-1 isolates correlate with phenotypic changes, different EBLV-1 variants were compared for pathogenicity in the mouse model. Groups of three mice were infected intracranially (i.c.) with 102 TCID50/ml and groups of six mice were infected intramuscularly (i.m.) with 105 TCID50/ml and 102 TCID50/ml as well as intranasally (i.n.) with 102 TCID50/ml. Significant differences in survival following i.m. inoculation with low doses as well as i.n. inoculation were observed. Also, striking variations in incubation periods following i.c. inoculation and i.m. inoculation with high doses were seen. Hereby, the clinical picture differed between general symptoms, spasms and aggressiveness depending on the inoculation route. Immunohistochemistry of mouse brains showed that the virus distribution in the brain depended on the inoculation route. In conclusion, different EBLV-1 isolates differ in pathogenicity indicating variation which is not reflected in studies of single isolates.
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Project description:Transcriptomic responses of bat cells to European bat lyssavirus 1 infection under conditions simulating euthermia and hibernation
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Project description:Characterization of the novel Kotalahti bat lyssavirus
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Project description:Enhanced Bat Lyssavirus Surveillance in Germany between 2018-2020
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Project description:Full-genome Sequences and Phylogenetic Analysis of Archived Danish European Bat Lyssavirus 1 (EBLV-1) Emphasize a Higher Genetic Resolution and Spatial Segregation for Sublineage 1a
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Project description:Rabies lyssavirus bat related - Genome sequencing and assembly
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Project description:Among lyssaviruses, West Caucasian bat virus (WCBV) and Lleida bat lyssavirus (LLEBV) raise concern as their divergence from rabies virus leads to the inefficacy of available prophylactic agents. Both viruses were described in the bat Miniopterus schreibersii. We investigated the European distribution of WCBV and LLEBV by screening sera from Miniopterus schreibersii across eight countries, finding widespread serological evidence and positivity up to 70%. We evaluated the intramuscular lethality of wild type isolates in Syrian hamsters. WCBV induced 100% lethality and a clinical disease compatible with furious rabies. All animals infected with LLEBV remained healthy for 40 days, despite one individual testing positive in the brain. We confirmed LLEBV's intramuscular a-pathogenicity using mice. Infected hamsters developed antibodies by day seven, regardless the virus and the clinical outcome. This study highlights the widespread circulation of WCBV and LLEBV in Europe and suggests differences in neuro-invasiveness and/or pathogenesis that are crucial for risk assessment.
| S-EPMC11787528 | biostudies-literature
Project description:Data from the VLA lyssavirus genotyping microarray. The array platform for this data is GEO accession GPL8066, and consists of 624 oligos representing two viral families. The data set itself consists of 14 arrays, 7 hybridised with RNA from mice brains infected with 7 genotypes of lyssaviruses, 1 hybridised with RNA from normal mouse brain, and 6 hybridised with RNA from coded samples consisting of infected mouse brains or control mouse brains. Keywords: Lyssavirus genotyping microarray
2009-06-09 | GSE14705 | GEO
Project description:Surveillance for rabies-related lyssaviruses in South African insectivorous bat species
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