Genotype-driven sensitivity of mice to tick-borne encephalitis virus correlates with differential host responses in peripheral macrophages and brain
Abstract Background Tick-borne encephalitis (TBE) is the most common tick-borne viral infection in Eurasia. Outcomes range from asymptomatic infection to fatal encephalitis, with host genetics likely playing a role. BALB/c mice have intermediate susceptibility to TBE virus (TBEV) and STS mice are hi...
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BMC
2025-01-01
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| Series: | Journal of Neuroinflammation |
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| Online Access: | https://doi.org/10.1186/s12974-025-03354-1 |
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| author | Michaela Berankova Jiri Holoubek Vaclav Hönig Zuzana Matusova Martin Palus Jiri Salat Imtissal Krayem Jarmila Vojtiskova Pavel Svoboda Veronika Pranclova Lukas Valihrach Peter Demant Marie Lipoldova Daniel Ruzek |
| author_facet | Michaela Berankova Jiri Holoubek Vaclav Hönig Zuzana Matusova Martin Palus Jiri Salat Imtissal Krayem Jarmila Vojtiskova Pavel Svoboda Veronika Pranclova Lukas Valihrach Peter Demant Marie Lipoldova Daniel Ruzek |
| author_sort | Michaela Berankova |
| collection | DOAJ |
| description | Abstract Background Tick-borne encephalitis (TBE) is the most common tick-borne viral infection in Eurasia. Outcomes range from asymptomatic infection to fatal encephalitis, with host genetics likely playing a role. BALB/c mice have intermediate susceptibility to TBE virus (TBEV) and STS mice are highly resistant, whereas the recombinant congenic strain CcS-11, which carries 12.5% of the STS genome on the BALB/c background, is more susceptible than BALB/c mice. In the present study, we employed these genetically distinct mouse models to investigate the host response to TBEV infection in both peripheral macrophages, one of the initial target cell populations, and the brain, the terminal target organ of the virus. Methods TBEV growth and the production of key cytokines and chemokines were measured and compared in macrophages derived from BALB/c, CcS-11, and STS mice. In addition, brains from these TBEV-infected mouse strains underwent in-depth transcriptomic analysis. Results Virus production in BALB/c and CcS-11 macrophages exhibited similar kinetics 24 and 48 h post-infection (hpi), but CcS-11 macrophages yielded significantly higher titers 72 hpi. Macrophages from both sensitive strains demonstrated elevated chemokine and proinflammatory cytokine production upon infection, whereas the resistant strain, STS, showed no cytokine/chemokine activation. Transcriptomic analysis of brain tissue demonstrated that the genetic background of the mouse strains dictated their transcriptional response to infection. The resistant strain exhibited a more robust cell-mediated immune response, whereas both sensitive strains showed a less effective cell-mediated response but increased cytokine signaling and signs of demyelination, with loss of oligodendrocytes. Conclusions Our findings suggest that variations in susceptibility linked to host genetic background correspond with distinct host responses, both in the periphery upon virus entry into the organism and in the brain, the target organ of the virus. These results provide insights into the influence of host genetics on the clinical trajectory of TBE. |
| format | Article |
| id | doaj-art-c22276bd18bb482881a5e4e7cf9c015d |
| institution | Kabale University |
| issn | 1742-2094 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj-art-c22276bd18bb482881a5e4e7cf9c015d2025-02-02T12:35:04ZengBMCJournal of Neuroinflammation1742-20942025-01-0122111710.1186/s12974-025-03354-1Genotype-driven sensitivity of mice to tick-borne encephalitis virus correlates with differential host responses in peripheral macrophages and brainMichaela Berankova0Jiri Holoubek1Vaclav Hönig2Zuzana Matusova3Martin Palus4Jiri Salat5Imtissal Krayem6Jarmila Vojtiskova7Pavel Svoboda8Veronika Pranclova9Lukas Valihrach10Peter Demant11Marie Lipoldova12Daniel Ruzek13Department of Experimental Biology, Faculty of Science, Masaryk UniversityDepartment of Experimental Biology, Faculty of Science, Masaryk UniversityLaboratory of Arbovirology, Institute of Parasitology, Biology Centre of the Czech Academy of SciencesLaboratory of Gene Expression, Institute of Biotechnology of the Czech Academy of SciencesLaboratory of Arbovirology, Institute of Parasitology, Biology Centre of the Czech Academy of SciencesLaboratory of Arbovirology, Institute of Parasitology, Biology Centre of the Czech Academy of SciencesLaboratory of Molecular and Cellular Immunology, Institute of Molecular Genetics, Czech Academy of SciencesLaboratory of Molecular and Cellular Immunology, Institute of Molecular Genetics, Czech Academy of SciencesLaboratory of Emerging Viral Diseases, Veterinary Research InstituteLaboratory of Arbovirology, Institute of Parasitology, Biology Centre of the Czech Academy of SciencesLaboratory of Gene Expression, Institute of Biotechnology of the Czech Academy of SciencesDepartment of Molecular and Cellular Biology, Roswell Park Comprehensive Cancer CenterLaboratory of Molecular and Cellular Immunology, Institute of Molecular Genetics, Czech Academy of SciencesDepartment of Experimental Biology, Faculty of Science, Masaryk UniversityAbstract Background Tick-borne encephalitis (TBE) is the most common tick-borne viral infection in Eurasia. Outcomes range from asymptomatic infection to fatal encephalitis, with host genetics likely playing a role. BALB/c mice have intermediate susceptibility to TBE virus (TBEV) and STS mice are highly resistant, whereas the recombinant congenic strain CcS-11, which carries 12.5% of the STS genome on the BALB/c background, is more susceptible than BALB/c mice. In the present study, we employed these genetically distinct mouse models to investigate the host response to TBEV infection in both peripheral macrophages, one of the initial target cell populations, and the brain, the terminal target organ of the virus. Methods TBEV growth and the production of key cytokines and chemokines were measured and compared in macrophages derived from BALB/c, CcS-11, and STS mice. In addition, brains from these TBEV-infected mouse strains underwent in-depth transcriptomic analysis. Results Virus production in BALB/c and CcS-11 macrophages exhibited similar kinetics 24 and 48 h post-infection (hpi), but CcS-11 macrophages yielded significantly higher titers 72 hpi. Macrophages from both sensitive strains demonstrated elevated chemokine and proinflammatory cytokine production upon infection, whereas the resistant strain, STS, showed no cytokine/chemokine activation. Transcriptomic analysis of brain tissue demonstrated that the genetic background of the mouse strains dictated their transcriptional response to infection. The resistant strain exhibited a more robust cell-mediated immune response, whereas both sensitive strains showed a less effective cell-mediated response but increased cytokine signaling and signs of demyelination, with loss of oligodendrocytes. Conclusions Our findings suggest that variations in susceptibility linked to host genetic background correspond with distinct host responses, both in the periphery upon virus entry into the organism and in the brain, the target organ of the virus. These results provide insights into the influence of host genetics on the clinical trajectory of TBE.https://doi.org/10.1186/s12974-025-03354-1Tick-borne encephalitisTick-borne encephalitis virusMouse modelNeuroinflammationGeneticsTranscriptomics |
| spellingShingle | Michaela Berankova Jiri Holoubek Vaclav Hönig Zuzana Matusova Martin Palus Jiri Salat Imtissal Krayem Jarmila Vojtiskova Pavel Svoboda Veronika Pranclova Lukas Valihrach Peter Demant Marie Lipoldova Daniel Ruzek Genotype-driven sensitivity of mice to tick-borne encephalitis virus correlates with differential host responses in peripheral macrophages and brain Journal of Neuroinflammation Tick-borne encephalitis Tick-borne encephalitis virus Mouse model Neuroinflammation Genetics Transcriptomics |
| title | Genotype-driven sensitivity of mice to tick-borne encephalitis virus correlates with differential host responses in peripheral macrophages and brain |
| title_full | Genotype-driven sensitivity of mice to tick-borne encephalitis virus correlates with differential host responses in peripheral macrophages and brain |
| title_fullStr | Genotype-driven sensitivity of mice to tick-borne encephalitis virus correlates with differential host responses in peripheral macrophages and brain |
| title_full_unstemmed | Genotype-driven sensitivity of mice to tick-borne encephalitis virus correlates with differential host responses in peripheral macrophages and brain |
| title_short | Genotype-driven sensitivity of mice to tick-borne encephalitis virus correlates with differential host responses in peripheral macrophages and brain |
| title_sort | genotype driven sensitivity of mice to tick borne encephalitis virus correlates with differential host responses in peripheral macrophages and brain |
| topic | Tick-borne encephalitis Tick-borne encephalitis virus Mouse model Neuroinflammation Genetics Transcriptomics |
| url | https://doi.org/10.1186/s12974-025-03354-1 |
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