Astrocyte Infection during Rabies Encephalitis Depends on the Virus Strain and Infection Route as Demonstrated by Novel Quantitative 3D Analysis of Cell Tropism
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 diffe...
| 主要な著者: | , , , , , , , , |
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| フォーマット: | 論文 |
| 言語: | English |
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MDPI AG
2020-02-01
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| シリーズ: | Cells |
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| オンライン･アクセス: | https://www.mdpi.com/2073-4409/9/2/412 |
| _version_ | 1827854184669511680 |
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| author | Madlin Potratz Luca Zaeck Michael Christen Verena te Kamp Antonia Klein Tobias Nolden Conrad M. Freuling Thomas Müller Stefan Finke |
| author_facet | Madlin Potratz Luca Zaeck Michael Christen Verena te Kamp Antonia Klein Tobias Nolden Conrad M. Freuling Thomas Müller Stefan Finke |
| author_sort | Madlin Potratz |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T11:16:57Z |
| format | Article |
| id | doaj.art-9db08b51a8bd471b80707b6d041387b7 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T11:16:57Z |
| publishDate | 2020-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-9db08b51a8bd471b80707b6d041387b72023-09-02T01:53:25ZengMDPI AGCells2073-44092020-02-019241210.3390/cells9020412cells9020412Astrocyte Infection during Rabies Encephalitis Depends on the Virus Strain and Infection Route as Demonstrated by Novel Quantitative 3D Analysis of Cell TropismMadlin Potratz0Luca Zaeck1Michael Christen2Verena te Kamp3Antonia Klein4Tobias Nolden5Conrad M. Freuling6Thomas Müller7Stefan Finke8Friedrich-Loeffler-Institut (FLI), Federal Research Institute for Animal Health, Institute of Molecular Virology and Cell Biology, 17493 Greifswald-Insel Riems, GermanyFriedrich-Loeffler-Institut (FLI), Federal Research Institute for Animal Health, Institute of Molecular Virology and Cell Biology, 17493 Greifswald-Insel Riems, GermanyFriedrich-Loeffler-Institut (FLI), Federal Research Institute for Animal Health, Institute of Molecular Virology and Cell Biology, 17493 Greifswald-Insel Riems, GermanyThescon GmbH, 48653 Coesfeld, GermanyFriedrich-Loeffler-Institut (FLI), Federal Research Institute for Animal Health, Institute of Molecular Virology and Cell Biology, 17493 Greifswald-Insel Riems, GermanyViraTherapeutics GmbH, 6020 Innsbruck, AustriaFriedrich-Loeffler-Institut (FLI), Federal Research Institute for Animal Health, Institute of Molecular Virology and Cell Biology, 17493 Greifswald-Insel Riems, GermanyFriedrich-Loeffler-Institut (FLI), Federal Research Institute for Animal Health, Institute of Molecular Virology and Cell Biology, 17493 Greifswald-Insel Riems, GermanyFriedrich-Loeffler-Institut (FLI), Federal Research Institute for Animal Health, Institute of Molecular Virology and Cell Biology, 17493 Greifswald-Insel Riems, GermanyAlthough 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.https://www.mdpi.com/2073-4409/9/2/412rabiesudisco3d imagingrabies pathogenicityastrocyte infection |
| spellingShingle | Madlin Potratz Luca Zaeck Michael Christen Verena te Kamp Antonia Klein Tobias Nolden Conrad M. Freuling Thomas Müller Stefan Finke Astrocyte Infection during Rabies Encephalitis Depends on the Virus Strain and Infection Route as Demonstrated by Novel Quantitative 3D Analysis of Cell Tropism Cells rabies udisco 3d imaging rabies pathogenicity astrocyte infection |
| title | Astrocyte Infection during Rabies Encephalitis Depends on the Virus Strain and Infection Route as Demonstrated by Novel Quantitative 3D Analysis of Cell Tropism |
| title_full | Astrocyte Infection during Rabies Encephalitis Depends on the Virus Strain and Infection Route as Demonstrated by Novel Quantitative 3D Analysis of Cell Tropism |
| title_fullStr | Astrocyte Infection during Rabies Encephalitis Depends on the Virus Strain and Infection Route as Demonstrated by Novel Quantitative 3D Analysis of Cell Tropism |
| title_full_unstemmed | Astrocyte Infection during Rabies Encephalitis Depends on the Virus Strain and Infection Route as Demonstrated by Novel Quantitative 3D Analysis of Cell Tropism |
| title_short | Astrocyte Infection during Rabies Encephalitis Depends on the Virus Strain and Infection Route as Demonstrated by Novel Quantitative 3D Analysis of Cell Tropism |
| title_sort | astrocyte infection during rabies encephalitis depends on the virus strain and infection route as demonstrated by novel quantitative 3d analysis of cell tropism |
| topic | rabies udisco 3d imaging rabies pathogenicity astrocyte infection |
| url | https://www.mdpi.com/2073-4409/9/2/412 |
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