Human endogenous retrovirus-K contributes to motor neuron disease

Wenxue Li, Myoung Hwa Lee, Lisa Henderson, Richa Tyagi, Muzna Bachani, Joseph Steiner, Emilie Campanac, Dax A. Hoffman, Gloria Von Geldern, Kory Johnson, Dragan Maric, H. Douglas Morris, Margaret Lentz, Katherine Pak, Andrew Mammen, Lyle Ostrow, Jeffrey D Rothstein, Avindra Nath

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalScience Translational Medicine
Volume7
Issue number307
DOIs
StatePublished - Sep 30 2015

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Endogenous Retroviruses
Motor Neuron Disease
Neurons
Amyotrophic Lateral Sclerosis
Anterior Horn Cells
Viruses
Dendritic Spines
Genetically Modified Animals
Muscular Atrophy
Terminal Repeat Sequences
Pyramidal Cells
Motor Cortex
DNA-Binding Proteins
Denervation
Neurites
Nerve Fibers
DNA Damage
Spinal Cord
Proteins
Wounds and Injuries

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Li, W., Lee, M. H., Henderson, L., Tyagi, R., Bachani, M., Steiner, J., ... Nath, A. (2015). Human endogenous retrovirus-K contributes to motor neuron disease. Science Translational Medicine, 7(307). https://doi.org/10.1126/scitranslmed.aac8201

Human endogenous retrovirus-K contributes to motor neuron disease. / Li, Wenxue; Lee, Myoung Hwa; Henderson, Lisa; Tyagi, Richa; Bachani, Muzna; Steiner, Joseph; Campanac, Emilie; Hoffman, Dax A.; Geldern, Gloria Von; Johnson, Kory; Maric, Dragan; Morris, H. Douglas; Lentz, Margaret; Pak, Katherine; Mammen, Andrew; Ostrow, Lyle; Rothstein, Jeffrey D; Nath, Avindra.

In: Science Translational Medicine, Vol. 7, No. 307, 30.09.2015.

Research output: Contribution to journalArticle

Li, W, Lee, MH, Henderson, L, Tyagi, R, Bachani, M, Steiner, J, Campanac, E, Hoffman, DA, Geldern, GV, Johnson, K, Maric, D, Morris, HD, Lentz, M, Pak, K, Mammen, A, Ostrow, L, Rothstein, JD & Nath, A 2015, 'Human endogenous retrovirus-K contributes to motor neuron disease', Science Translational Medicine, vol. 7, no. 307. https://doi.org/10.1126/scitranslmed.aac8201
Li, Wenxue ; Lee, Myoung Hwa ; Henderson, Lisa ; Tyagi, Richa ; Bachani, Muzna ; Steiner, Joseph ; Campanac, Emilie ; Hoffman, Dax A. ; Geldern, Gloria Von ; Johnson, Kory ; Maric, Dragan ; Morris, H. Douglas ; Lentz, Margaret ; Pak, Katherine ; Mammen, Andrew ; Ostrow, Lyle ; Rothstein, Jeffrey D ; Nath, Avindra. / Human endogenous retrovirus-K contributes to motor neuron disease. In: Science Translational Medicine. 2015 ; Vol. 7, No. 307.
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