Identification of active loci of a human endogenous retrovirus in neurons of patients with amyotrophic lateral sclerosis
Article first published online: 28 JAN 2011
Copyright © 2010 American Neurological Association
Annals of Neurology
Volume 69, Issue 1, pages 141–151, January 2011
How to Cite
Douville, R., Liu, J., Rothstein, J. and Nath, A. (2011), Identification of active loci of a human endogenous retrovirus in neurons of patients with amyotrophic lateral sclerosis. Ann Neurol., 69: 141–151. doi: 10.1002/ana.22149
- Issue published online: 28 JAN 2011
- Article first published online: 28 JAN 2011
- Accepted manuscript online: 8 NOV 2010 12:54PM EST
- Manuscript Accepted: 2 JUL 2010
- Manuscript Revised: 25 JUN 2010
- Manuscript Received: 24 MAR 2010
Amyotrophic lateral sclerosis (ALS) is characterized by the progressive loss of motor neurons, of unknown etiology. Previous studies showed reverse transcriptase in serum of ALS patients at levels comparable to human immunodeficiency virus-infected patients; however, the source and significance of the retroviral elements is uncertain.
Expression of a human endogenous retrovirus (HERV-K) was determined in autopsy brain tissue of patients with ALS and compared to control populations by real-time polymerase chain reaction followed by sequencing of the amplified genes and confirmed by immunostaining.
HERV-K pol transcripts were increased in patients with ALS compared to those with chronic systemic illness, but could not be detected in Parkinson disease or in the accidental death controls. Sequencing revealed several actively transcribed loci in the HML-2 and 3 subfamilies of HERV-K, with a specific pattern of expression including intact open reading frames and the transcription of a unique locus in ALS. The frequency of intact pol transcripts was highest in the motor cortex, and the reverse transcriptase protein was localized to cortical neurons of ALS patients. HERV-K expression strongly correlated with TDP-43, a multifunctional protein known to be dysregulated in ALS.
We have identified a specific pattern of HERV-K expression in ALS, which may potentially define the pathophysiology of ALS. Targeting of activated genome-encoded retroviral elements may open new prospects for the treatment of ALS. Ann Neurol 2011;69:141–151.