Endogenous retrovirus activation disrupts postsynaptic organization in human glutamatergic neurons
- 1Lund University
Abstract
Endogenous retroviruses (ERVs) comprise a substantial fraction of the human genome, yet whether their expression can directly alter human neuronal function remains unknown. Because glutamatergic signaling is fundamental to brain function and frequently disrupted in brain disorders, we asked whether activation of the primate-specific ERV-W group, associated with neurological disease, perturbs human glutamatergic neurons. We used CRISPR activation of the LTR17-ERV-W consensus sequence to examine its effects on neuronal and synaptic function, inducing transcription from multiple proviral loci, including five with intact open reading frames. Functionally, ERV-W activation selectively altered the postsynaptic compartment, reducing PSD-95 and NMDA receptor abundance. These changes were accompanied by altered excitatory synaptic transmission and reduced intrinsic excitability, whereas activation of ERVW-1/Syncytin-1 alone did not reproduce the phenotype. Our findings identify ERV-W activation as a modulator of human neuronal function with potential relevance to ERV-associated brain disorders.
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BibTeX
@misc{davishansson2026endogenous,
title = {{Endogenous retrovirus activation disrupts postsynaptic organization in human glutamatergic neurons}},
author = {C. Davis-Hansson and R. Garza and C. Piochon and J. G. Johansson and V. Busskamp and J. Jakobsson and E. M. Johansson},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.21.760639},
url = {https://www.biorxiv.org/content/10.64898/2026.10.21.760639v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Endogenous retrovirus activation disrupts postsynaptic organization in human glutamatergic neurons
AU - C. Davis-Hansson
AU - R. Garza
AU - C. Piochon
AU - J. G. Johansson
AU - V. Busskamp
AU - J. Jakobsson
AU - E. M. Johansson
PY - 2026
DA - 2026/10/21
PB - bioRxiv
DO - 10.64898/2026.10.21.760639
UR - https://www.biorxiv.org/content/10.64898/2026.10.21.760639v1
AB - Endogenous retroviruses (ERVs) comprise a substantial fraction of the human genome, yet whether their expression can directly alter human neuronal function remains unknown. Because glutamatergic signaling is fundamental to brain function and frequently disrupted in brain disorders, we asked whether activation of the primate-specific ERV-W group, associated with neurological disease, perturbs human glutamatergic neurons. We used CRISPR activation of the LTR17-ERV-W consensus sequence to examine its effects on neuronal and synaptic function, inducing transcription from multiple proviral loci, including five with intact open reading frames. Functionally, ERV-W activation selectively altered the postsynaptic compartment, reducing PSD-95 and NMDA receptor abundance. These changes were accompanied by altered excitatory synaptic transmission and reduced intrinsic excitability, whereas activation of ERVW-1/Syncytin-1 alone did not reproduce the phenotype. Our findings identify ERV-W activation as a modulator of human neuronal function with potential relevance to ERV-associated brain disorders.
ER -