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Open Access 01-12-2023 | Interferon | Research

Astrocytes evoke a robust IRF7-independent type I interferon response upon neurotropic viral infection

Authors: Loreen Weichert, Henning Peter Düsedau, David Fritzsch, Sarah Schreier, Annika Scharf, Martina Grashoff, Kristin Cebulski, Kristin Michaelsen-Preusse, Christian Erck, Stefan Lienenklaus, Ildiko Rita Dunay, Andrea Kröger

Published in: Journal of Neuroinflammation | Issue 1/2023

Abstract

Background

Type I interferons (IFN-I) are fundamental in controlling viral infections but fatal interferonopathy is restricted in the immune-privileged central nervous system (CNS). In contrast to the well-established role of Interferon Regulatory Factor 7 (IRF7) in the regulation of IFN-I response in the periphery, little is known about the specific function in the CNS.

Methods

To investigate the role for IRF7 in antiviral response during neurotropic virus infection, mice deficient for IRF3 and IRF7 were infected systemically with Langat virus (LGTV). Viral burden and IFN-I response was analyzed in the periphery and the CNS by focus formation assay, RT-PCR, immunohistochemistry and in vivo imaging. Microglia and infiltration of CNS-infiltration of immune cells were characterized by flow cytometry.

Results

Here, we demonstrate that during infection with the neurotropic Langat virus (LGTV), an attenuated member of the tick-borne encephalitis virus (TBEV) subgroup, neurons do not rely on IRF7 for cell-intrinsic antiviral resistance and IFN-I induction. An increased viral replication in IRF7-deficient mice suggests an indirect antiviral mechanism. Astrocytes rely on IRF7 to establish a cell-autonomous antiviral response. Notably, the loss of IRF7 particularly in astrocytes resulted in a high IFN-I production. Sustained production of IFN-I in astrocytes is independent of an IRF7-mediated positive feedback loop.

Conclusion

IFN-I induction in the CNS is profoundly regulated in a cell type-specific fashion.

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Title: Astrocytes evoke a robust IRF7-independent type I interferon response upon neurotropic viral infection
Authors: Loreen Weichert
Henning Peter Düsedau
David Fritzsch
Sarah Schreier
Annika Scharf
Martina Grashoff
Kristin Cebulski
Kristin Michaelsen-Preusse
Christian Erck
Stefan Lienenklaus
Ildiko Rita Dunay
Andrea Kröger
Publication date: 01-12-2023
Publisher: BioMed Central
Keyword: Interferon
Published in: Journal of Neuroinflammation / Issue 1/2023
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/s12974-023-02892-w

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Astrocytes evoke a robust IRF7-independent type I interferon response upon neurotropic viral infection

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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