Astrocyte Infection during Rabies Encephalitis Depends on the Virus Strain and Infection Route as Demonstrated by Novel Quantitative 3D Analysis of Cell Tropism.

Autor: Potratz M; Friedrich-Loeffler-Institut (FLI), Federal Research Institute for Animal Health, Institute of Molecular Virology and Cell Biology, 17493 Greifswald-Insel Riems, Germany., Zaeck L; Friedrich-Loeffler-Institut (FLI), Federal Research Institute for Animal Health, Institute of Molecular Virology and Cell Biology, 17493 Greifswald-Insel Riems, Germany., Christen M; Friedrich-Loeffler-Institut (FLI), Federal Research Institute for Animal Health, Institute of Molecular Virology and Cell Biology, 17493 Greifswald-Insel Riems, Germany., Te Kamp V; Thescon GmbH, 48653 Coesfeld, Germany., Klein A; Friedrich-Loeffler-Institut (FLI), Federal Research Institute for Animal Health, Institute of Molecular Virology and Cell Biology, 17493 Greifswald-Insel Riems, Germany., Nolden T; ViraTherapeutics GmbH, 6020 Innsbruck, Austria., Freuling CM; Friedrich-Loeffler-Institut (FLI), Federal Research Institute for Animal Health, Institute of Molecular Virology and Cell Biology, 17493 Greifswald-Insel Riems, Germany., Müller T; Friedrich-Loeffler-Institut (FLI), Federal Research Institute for Animal Health, Institute of Molecular Virology and Cell Biology, 17493 Greifswald-Insel Riems, Germany., Finke S; Friedrich-Loeffler-Institut (FLI), Federal Research Institute for Animal Health, Institute of Molecular Virology and Cell Biology, 17493 Greifswald-Insel Riems, Germany.
Jazyk: angličtina
Zdroj: Cells [Cells] 2020 Feb 11; Vol. 9 (2). Date of Electronic Publication: 2020 Feb 11.
DOI: 10.3390/cells9020412
Abstrakt: Although conventional immunohistochemistry for neurotropic rabies virus (RABV) usually shows high preference for neurons, non-neuronal cells are also potential targets, and abortive astrocyte infection is considered a main trigger of innate immunity in the CNS. While in vitro studies indicated differences between field and less virulent lab-adapted RABVs, a systematic, quantitative comparison of astrocyte tropism in vivo is lacking. Here, solvent-based tissue clearing was used to measure RABV cell tropism in infected brains. Immunofluorescence analysis of 1 mm-thick tissue slices enabled 3D-segmentation and quantification of astrocyte and neuron infection frequencies. Comparison of three highly virulent field virus clones from fox, dog, and raccoon with three lab-adapted strains revealed remarkable differences in the ability to infect astrocytes in vivo. While all viruses and infection routes led to neuron infection frequencies between 7-19%, striking differences appeared for astrocytes. Whereas astrocyte infection by field viruses was detected independent of the inoculation route (8-27%), only one lab-adapted strain infected astrocytes route-dependently [0% after intramuscular (i.m.) and 13% after intracerebral (i.c.) inoculation]. Two lab-adapted vaccine viruses lacked astrocyte infection altogether (0%, i.c. and i.m.). This suggests a model in which the ability to establish productive astrocyte infection in vivo functionally distinguishes field and attenuated lab RABV strains.
Competing Interests: The authors declare no conflict of interest.
Databáze: MEDLINE
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