{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T07:09:46Z","timestamp":1791529786090,"version":"4.3.4"},"reference-count":61,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,2,11]],"date-time":"2020-02-11T00:00:00Z","timestamp":1581379200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Federal Excellence Initiative of Mecklenburg Western Pomerania and European Social Fund (ESF) Grant KoInfekt","award":["ESF\/14-BM-A55-0002\/16"],"award-info":[{"award-number":["ESF\/14-BM-A55-0002\/16"]}]},{"name":"Intramural collaborative research grant on Lyssaviruses at the Friedrich-Loeffler-Institute (FLI)","award":["Ri-0372"],"award-info":[{"award-number":["Ri-0372"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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\u201319%, striking differences appeared for astrocytes. Whereas astrocyte infection by field viruses was detected independent of the inoculation route (8\u201327%), 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.<\/jats:p>","DOI":"10.3390\/cells9020412","type":"journal-article","created":{"date-parts":[[2020,2,11]],"date-time":"2020-02-11T11:45:30Z","timestamp":1581421530000},"page":"412","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Astrocyte Infection during Rabies Encephalitis Depends on the Virus Strain and Infection Route as Demonstrated by Novel Quantitative 3D Analysis of Cell Tropism"],"prefix":"10.3390","volume":"9","author":[{"given":"Madlin","family":"Potratz","sequence":"first","affiliation":[{"name":"Friedrich-Loeffler-Institut (FLI), Federal Research Institute for Animal Health, Institute of Molecular Virology and Cell Biology, 17493 Greifswald-Insel Riems, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7997-493X","authenticated-orcid":false,"given":"Luca","family":"Zaeck","sequence":"additional","affiliation":[{"name":"Friedrich-Loeffler-Institut (FLI), Federal Research Institute for Animal Health, Institute of Molecular Virology and Cell Biology, 17493 Greifswald-Insel Riems, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Christen","sequence":"additional","affiliation":[{"name":"Friedrich-Loeffler-Institut (FLI), Federal Research Institute for Animal Health, Institute of Molecular Virology and Cell Biology, 17493 Greifswald-Insel Riems, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena","family":"te Kamp","sequence":"additional","affiliation":[{"name":"Thescon GmbH, 48653 Coesfeld, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Klein","sequence":"additional","affiliation":[{"name":"Friedrich-Loeffler-Institut (FLI), Federal Research Institute for Animal Health, Institute of Molecular Virology and Cell Biology, 17493 Greifswald-Insel Riems, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8996-5612","authenticated-orcid":false,"given":"Tobias","family":"Nolden","sequence":"additional","affiliation":[{"name":"ViraTherapeutics GmbH, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1076-398X","authenticated-orcid":false,"given":"Conrad M.","family":"Freuling","sequence":"additional","affiliation":[{"name":"Friedrich-Loeffler-Institut (FLI), Federal Research Institute for Animal Health, Institute of Molecular Virology and Cell Biology, 17493 Greifswald-Insel Riems, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0959-3653","authenticated-orcid":false,"given":"Thomas","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Friedrich-Loeffler-Institut (FLI), Federal Research Institute for Animal Health, Institute of Molecular Virology and Cell Biology, 17493 Greifswald-Insel Riems, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8716-2341","authenticated-orcid":false,"given":"Stefan","family":"Finke","sequence":"additional","affiliation":[{"name":"Friedrich-Loeffler-Institut (FLI), Federal Research Institute for Animal Health, Institute of Molecular Virology and Cell Biology, 17493 Greifswald-Insel Riems, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17091","DOI":"10.1038\/nrdp.2017.91","article-title":"Rabies","volume":"3","author":"Fooks","year":"2017","journal-title":"Nat. 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