Human endogenous retrovirus-K contributes to motor neuron disease
- PMID: 26424568
- PMCID: PMC6344353
- DOI: 10.1126/scitranslmed.aac8201
Human endogenous retrovirus-K contributes to motor neuron disease
Abstract
The role of human endogenous retroviruses (HERVs) in disease pathogenesis is unclear. We show that HERV-K is activated in a subpopulation of patients with sporadic amyotrophic lateral sclerosis (ALS) and that its envelope (env) protein may contribute to neurodegeneration. The virus was expressed in cortical and spinal neurons of ALS patients, but not in neurons from control healthy individuals. Expression of HERV-K or its env protein in human neurons caused retraction and beading of neurites. Transgenic animals expressing the env gene developed progressive motor dysfunction accompanied by selective loss of volume of the motor cortex, decreased synaptic activity in pyramidal neurons, dendritic spine abnormalities, nucleolar dysfunction, and DNA damage. Injury to anterior horn cells in the spinal cord was manifested by muscle atrophy and pathological changes consistent with nerve fiber denervation and reinnervation. Expression of HERV-K was regulated by TAR (trans-activation responsive) DNA binding protein 43, which binds to the long terminal repeat region of the virus. Thus, HERV-K expression within neurons of patients with ALS may contribute to neurodegeneration and disease pathogenesis.
Copyright © 2015, American Association for the Advancement of Science.
Conflict of interest statement
Figures
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Comment in
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Endogenous retroviruses in ALS: A reawakening?Sci Transl Med. 2015 Sep 30;7(307):307fs40. doi: 10.1126/scitranslmed.aad3533. Sci Transl Med. 2015. PMID: 26424566 No abstract available.
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Motor neuron disease: Human endogenous retrovirus-K activation is implicated in amyotrophic lateral sclerosis.Nat Rev Neurol. 2015 Dec;11(12):666. doi: 10.1038/nrneurol.2015.206. Epub 2015 Oct 20. Nat Rev Neurol. 2015. PMID: 26481297 No abstract available.
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