Tumor Necrosis Factor-α Receptor 1 Mediates Borna Disease Virus 1-Induced Changes in Peroxisomal and Mitochondrial Dynamics in Neurons

Dominic Osei; Eveline Baumgart-Vogt; Barbara Ahlemeyer; Christiane Herden

doi:10.3390/ijms25031849

Tumor Necrosis Factor-α Receptor 1 Mediates Borna Disease Virus 1-Induced Changes in Peroxisomal and Mitochondrial Dynamics in Neurons

Int J Mol Sci. 2024 Feb 3;25(3):1849. doi: 10.3390/ijms25031849.

Authors

Dominic Osei^{1

2}, Eveline Baumgart-Vogt¹, Barbara Ahlemeyer¹, Christiane Herden^{2

3}

Affiliations

¹ Institute for Anatomy and Cell Biology, Justus Liebig University Giessen, 35392 Giessen, Germany.
² Institute of Veterinary Pathology, Justus Liebig University Giessen, 35392 Giessen, Germany.
³ Center for Mind, Brain and Behavior, Justus Liebig University Giessen, 35392 Giessen, Germany.

Abstract

Borna disease virus 1 (BoDV1) causes a persistent infection in the mammalian brain. Peroxisomes and mitochondria play essential roles in the cellular antiviral immune response, but the effect of BoDV1 infection on peroxisomal and mitochondrial dynamics and their respective antioxidant capacities is still not clear. Using different mouse lines-i.e., tumor necrosis factor-α transgenic (TNFTg; to pro-inflammatory status), TNF receptor-1 knockout (TNFR1ko), and TNFR2ko mice in comparison to wild-type (Wt) mice-we analyzed the abundances of both organelles and their main antioxidant enzymes, catalase and superoxide dismutase 2 (SOD2), in neurons of the hippocampal, cerebral, and cerebellar cortices. In TNFTg mice, a strong increase in mitochondrial (6.9-fold) and SOD2 (12.1-fold) abundances was detected; meanwhile, peroxisomal abundance increased slightly (1.5-fold), but that of catalase decreased (2.9-fold). After BoDV1 infection, a strong decrease in mitochondrial (2.1-6.5-fold), SOD2 (2.7-9.1-fold), and catalase (2.7-10.3-fold) abundances, but a slight increase in peroxisomes (1.3-1.6-fold), were detected in Wt and TNFR2ko mice, whereas no changes occurred in TNFR1ko mice. Our data suggest that the TNF system plays a crucial role in the biogenesis of both subcellular organelles. Moreover, TNFR1 signaling mediated the changes in peroxisomal and mitochondrial dynamics after BoDV1 infection, highlighting new mechanisms by which BoDV1 may achieve immune evasion and viral persistence.

Keywords: Borna disease virus 1; SOD2; TNF; TNFR1; TNFR2; brain; catalase; mitochondria; peroxisomes; persistent infection.

MeSH terms

Animals
Antioxidants
Borna disease virus*
Catalase / genetics
Mammals
Mice
Mice, Inbred C57BL
Mice, Knockout
Mitochondrial Dynamics
Neurons
Receptors, Tumor Necrosis Factor, Type I* / genetics
Tumor Necrosis Factor-alpha / physiology

Substances

Receptors, Tumor Necrosis Factor, Type I
Tumor Necrosis Factor-alpha
Catalase
Antioxidants

Grants and funding

D.O. received financial support from the Graduate School Scholarship Program of the German Academic Exchange Service (GSSP DAAD; Ref. No.: 91704103). Funding entity played no role in the design of this study, data collection and analyses, decision to publish findings or drafting of this manuscript.