| First Author | Weichert L | Year | 2023 |
| Journal | J Neuroinflammation | Volume | 20 |
| Issue | 1 | Pages | 213 |
| PubMed ID | 37737190 | Mgi Jnum | J:340751 |
| Mgi Id | MGI:7530269 | Doi | 10.1186/s12974-023-02892-w |
| Citation | Weichert L, et al. (2023) Astrocytes evoke a robust IRF7-independent type I interferon response upon neurotropic viral infection. J Neuroinflammation 20(1):213 |
| abstractText | 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. |
