Three-dimensional mapping of tick-borne encephalitis virus distribution in the mouse brain using a newly engineered TurboGFP reporter virus

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Authors

BERÁNKOVÁ Michaela LEONI Simone HOLOUBEK Jiří HAVIERNIK Jan SALÁT Jiří GRANDGIRARD Denis LEIB Stephen L RŮŽEK Daniel

Year of publication 2025
Type Article in Periodical
Magazine / Source Emerging Microbes and Infections
MU Faculty or unit

Faculty of Science

Citation
web https://doi.org/10.1080/22221751.2025.2542246
Doi https://doi.org/10.1080/22221751.2025.2542246
Keywords TBEV; reporter viruses; neurotropism; organotypic cerebellar slices; light-sheet microscopy; tissue clearing
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Description Tick-borne encephalitis virus (TBEV) is a neurotropic orthoflavivirus that invades the central nervous system, leading to severe neurological manifestations. In this study, we developed a reporter virus comprising TurboGFP-expressing TBEV (tGFP-TBEV) as a versatile tool for advancing TBEV research. The tGFP-TBEV facilitates quantitative measurement of viral replication, enables precise tracking of individual infected cells, and supports high-throughput screening of potential antiviral compounds and virus-neutralization assays. Furthermore, tGFP-TBEV proved effective as a model for studying TBEV infection in rat organotypic cerebellar slices cultured ex vivo and for visualizing TBEV infection in the mouse brain. Using tissue-clearing protocols and light-sheet fluorescence microscopy, we achieved high-resolution, three-dimensional mapping of the TBEV distribution in the mouse brain. This analysis uncovered distinct patterns of TBEV tropism, with infections concentrated in regions associated with neurogenesis, olfactory processing, and specific neuroanatomical pathways. The ability to visualize infection at both the cellular and whole-organ level provides a new tool for detailed investigations into viral tropism, replication, and interactions with host tissues, paving the way for deeper insights into TBEV biology and the pathogenesis of tick-borne encephalitis.
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