Identification of active loci of a human endogenous retrovirus in neurons of patients with amyotrophic lateral sclerosis

Objective 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 signifi...

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Bibliographic Details
Published in:	Annals of neurology Vol. 69; no. 1; pp. 141 - 151
Main Authors:	Douville, Renée, Liu, Jiankai, Rothstein, Jeffrey, Nath, Avindra
Format:	Journal Article
Language:	English
Published:	Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.01.2011 Wiley-Liss Wiley Subscription Services, Inc
Subjects:	Aged Aged, 80 and over Amyotrophic lateral sclerosis Amyotrophic Lateral Sclerosis - genetics Amyotrophic Lateral Sclerosis - physiopathology Amyotrophic Lateral Sclerosis - virology Biological and medical sciences Brain - physiopathology Brain - virology Cerebral Cortex - physiopathology Cerebral Cortex - virology Cytogenetics Endogenous Retroviruses - genetics Endogenous Retroviruses - isolation & purification Female Gene Expression Gene Frequency - genetics HIV Human endogenous retrovirus Human immunodeficiency virus Humans Male Medical sciences Middle Aged Motor Neurons - virology Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis Neurology Neurons Reverse Transcriptase Polymerase Chain Reaction - statistics & numerical data RNA, Messenger - genetics Transcriptional Activation - physiology Viral Proteins - genetics Human Nervous system diseases Neuron Central nervous system disease Amyotrophic lateral sclerosis Degenerative disease Spinal cord disease
ISSN:	0364-5134, 1531-8249, 1531-8249
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Summary:	Objective 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. Methods 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. Results 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. Interpretation 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.
Bibliography:	ark:/67375/WNG-HJWPT64M-F istex:8E43058FA08DC808E52114BA150039EBE730D0AE ArticleID:ANA22149 ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 14 content type line 23
ISSN:	0364-5134 1531-8249 1531-8249
DOI:	10.1002/ana.22149