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

Madlin Potratz, Luca Zaeck, Michael Christen, Verena Te Kamp, Antonia Klein, Tobias Nolden, Conrad M. Freuling, Thomas Müller, Stefan Finke*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

28 Citations (Scopus)
9 Downloads (Pure)

Abstract

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.

Original languageEnglish
JournalCells
Volume9
Issue number2
DOIs
Publication statusPublished - 11 Feb 2020
Externally publishedYes

Bibliographical note

Funding:
This work was funded by an intramural collaborative research grant on Lyssaviruses at the
Friedrich-Loeffler-Institute (Ri-0372) to S.F. and C.M.F. L.Z. was supported by the Federal Excellence Initiative of
Mecklenburg Western Pomerania and European Social Fund (ESF) Grant KoInfekt (ESF/14-BM-A55-0002/16).

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