Activation of endogenous retroviruses during brain development causes an inflammatory response
Open accessAbstract
Endogenous retroviruses (ERVs) make up a large fraction of mammalian genomes and are thought to contribute to human disease, including brain disorders. In the brain, aberrant activation of ERVs is a potential trigger for an inflammatory response, but mechanistic insight into this phenomenon remains lacking. Using CRISPR/Cas9-based gene disruption of the epigenetic co-repressor protein Trim28, we found a dynamic H3K9me3-dependent regulation of ERVs in proliferating neural progenitor cells (NPCs), but not in adult neurons. In vivo deletion of Trim28 in cortical NPCs during mouse brain development resulted in viable offspring expressing high levels of ERVs in excitatory neurons in the adult brain. Neuronal ERV expression was linked to activated microglia and the presence of ERV-derived proteins in aggregate-like structures. This study demonstrates that brain development is a critical period for the silencing of ERVs and provides causal in vivo evidence demonstrating that transcriptional activation of ERV in neurons results in an inflammatory response.
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Retrotransposon-encoded products, including viral-like proteins, double-stranded RNAs, and extrachromosomal circular DNAs, can be potent activators of the innate immune system.
“Retrotransposon-encoded products, including viral-like proteins, double-stranded RNAs, and extrachromosomal circular DNAs, can also be potent activators of the innate immune system.”
From The Role of Retrotransposons and Endogenous Retroviruses in Age-Dependent Neurodegenerative Disorders (2024) · cites this paper as Jönsson et al. 2021
The Results section (“ERV-derived proteins are found in areas of microglia activation”; page unavailable) says ERV-derived double-stranded RNA can activate innate immunity. The Discussion (page unavailable) proposes ERV-derived proteins as a possible cause of inflammation, but does not establish that mechanism; our copy does not address extrachromosomal circular DNA as an immune activator. (LLM, conf=0.87)
Experimental — accuracy not yet measuredCellular products generated over the life cycle of retrotransposon activation are subject to cellular detection and clearance through the innate immune system.
“Cellular products that are generated over the life cycle of retrotransposon activation are subject to cellular detection and clearance through the innate immune system”
From The Role of Retrotransposons and Endogenous Retroviruses in Age-Dependent Neurodegenerative Disorders (2024) · cites this paper as Jönsson et al. 2021
The Results section ('ERV-derived proteins are found in areas of microglia activation'; page not provided) says ERV-derived nucleic acids can activate innate immune detection. It does not establish that retrotransposon products generally undergo immune clearance; in the studied neural cells, the authors found no detectable interferon response despite ERV activation. (LLM, conf=0.85)
Experimental — accuracy not yet measured
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Comparing Contemporary Evangelical Models Regarding Human Origins
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Retroviral insertions contributed to the divergence of human and chimpanzee brainsPreprint
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Research progress of endogenous retroviruses in tumors and other human diseases
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Self-citationAere perennius: how chromatin fidelity is maintained and lost in disease
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The absence of Trim28 in nephron progenitors results in impaired kidney development and function
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Retroviral insertions contributed to the divergence of human and chimpanzee brains
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Self-citation
- Authors
- Jönsson, M. E., Garza, R., Sharma, Y., Petri, R., Södersten, E., Johansson, J. G., Johansson, P. A., Atacho, D. A., Pircs, K., Madsen, S., Yudovich, D., Ramakrishnan, R., Holmberg, J., Larsson, J., Jern, P., & Jakobsson, J.
- Affiliations
- Lund University (SE)
- Karolinska Institutet (SE)
- Uppsala University (SE)
- Corresponding author
- Jakobsson, Johan
- ORCID
- Venue
- The EMBO Journal
- Published
- 2021-03-01
- Volume
- 40
- Issue
- 9
- Pages
- e106423-e106423
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC8090857
- OpenAlex
- W3135617942
- Cited by
- 80
- References
- 87
- Citations by year
- 2026: 10 · 2025: 23 · 2024: 15 · 2023: 13 · 2022: 11 · 2021: 7 · 2020: 1
- FWCI
- 6.91
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- The EMBO Journal (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- KTH Publication Database DiVA (KTH Royal Institute of Technology) (submittedVersion, other-oa)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Vetenskapsrådet (2018‐02694, 2018‐03017)
- Hjärnfonden (FO2019‐0098)
- Cancerfonden (190326)
- Barncancerfonden (PR2017‐0053)
- Svenska Forskningsrådet Formas (2018‐01008)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- endogenous retroviruses, brain development, TRIM28, H3K9me3, neural progenitor cells, microglial activation, neuroinflammation, excitatory neurons, CRISPR/Cas9 gene disruption, cortical development
- MeSH terms
- Tripartite Motif-Containing Protein 28, Animals, Brain, Cells, Cultured, Encephalitis, Gene Expression Regulation, Histones, Transcriptional Activation, Gene Deletion, Endogenous Retroviruses, Epigenesis, Genetic, Mice, CRISPR-Cas Systems
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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