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 Rothstein, Avindra Nath

Research output: Contribution to journalArticlepeer-review

182 Scopus citations


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
Issue number307
StatePublished - Sep 30 2015

ASJC Scopus subject areas

  • General Medicine


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