Transcriptional profiling of HERV-K(HML-2) in amyotrophic lateral sclerosis and potential implications for expression of HML-2 proteins
Abstract Background Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder. About 90% of ALS cases are without a known genetic cause. The human endogenous retrovirus multi-copy HERV-K(HML-2) group was recently reported to potentially contribute to neurodegeneration and disease pat...
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doaj-a614b9b1c6a245569d81d26e1a7fc6ea2020-11-24T21:53:43ZengBMCMolecular Neurodegeneration1750-13262018-08-0113112510.1186/s13024-018-0275-3Transcriptional profiling of HERV-K(HML-2) in amyotrophic lateral sclerosis and potential implications for expression of HML-2 proteinsJens Mayer0Christian Harz1Laura Sanchez2Gavin C. Pereira3Esther Maldener4Sara R. Heras5Lyle W. Ostrow6John Ravits7Ranjan Batra8Eckart Meese9Jose Luis García-Pérez10John L. Goodier11Department of Human Genetics, University of SaarlandDepartment of Human Genetics, University of SaarlandGENYO. Centre for Genomics and Oncological Research: Pfizer, University of Granada, Andalusian Regional GovernmentMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of MedicineDepartment of Human Genetics, University of SaarlandGENYO. Centre for Genomics and Oncological Research: Pfizer, University of Granada, Andalusian Regional GovernmentDepartment of Neurology, Johns Hopkins University School of MedicineDepartment of Neurosciences, School of Medicine, UCSDDepartment of Neurosciences, School of Medicine, UCSDDepartment of Human Genetics, University of SaarlandGENYO. Centre for Genomics and Oncological Research: Pfizer, University of Granada, Andalusian Regional GovernmentMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of MedicineAbstract Background Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder. About 90% of ALS cases are without a known genetic cause. The human endogenous retrovirus multi-copy HERV-K(HML-2) group was recently reported to potentially contribute to neurodegeneration and disease pathogenesis in ALS because of transcriptional upregulation and toxic effects of HML-2 Envelope (Env) protein. Env and other proteins are encoded by some transcriptionally active HML-2 loci. However, more detailed information is required regarding which HML-2 loci are transcribed in ALS, which of their proteins are expressed, and differences between the disease and non-disease states. Methods For brain and spinal cord tissue samples from ALS patients and controls, we identified transcribed HML-2 loci by generating and mapping HML-2-specific cDNA sequences. We predicted expression of HML-2 env gene-derived proteins based on the observed cDNA sequences. Furthermore, we determined overall HML-2 transcript levels by RT-qPCR and investigated presence of HML-2 Env protein in ALS and control tissue samples by Western blotting. Results We identified 24 different transcribed HML-2 loci. Some of those loci are transcribed at relatively high levels. However, significant differences in HML-2 loci transcriptional activities were not seen when comparing ALS and controls. Likewise, overall HML-2 transcript levels, as determined by RT-qPCR, were not significantly different between ALS and controls. Indeed, we were unable to detect full-length HML-2 Env protein in ALS and control tissue samples despite reasonable sensitivity. Rather our analyses suggest that a number of HML-2 protein variants other than full-length Env may potentially be expressed in ALS patients. Conclusions Our results expand and refine recent publications on HERV-K(HML-2) and ALS. Some of our results are in conflict with recent findings and call for further specific analyses. Our profiling of HML-2 transcription in ALS opens up the possibility that HML-2 proteins other than canonical full-length Env may have to be considered when studying the role of HML-2 in ALS disease.http://link.springer.com/article/10.1186/s13024-018-0275-3Amyotrophic lateral sclerosisHuman endogenous retrovirusHERV-K(HML-2)RetrotransposonReverse transcriptionProvirus |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jens Mayer Christian Harz Laura Sanchez Gavin C. Pereira Esther Maldener Sara R. Heras Lyle W. Ostrow John Ravits Ranjan Batra Eckart Meese Jose Luis García-Pérez John L. Goodier |
spellingShingle |
Jens Mayer Christian Harz Laura Sanchez Gavin C. Pereira Esther Maldener Sara R. Heras Lyle W. Ostrow John Ravits Ranjan Batra Eckart Meese Jose Luis García-Pérez John L. Goodier Transcriptional profiling of HERV-K(HML-2) in amyotrophic lateral sclerosis and potential implications for expression of HML-2 proteins Molecular Neurodegeneration Amyotrophic lateral sclerosis Human endogenous retrovirus HERV-K(HML-2) Retrotransposon Reverse transcription Provirus |
author_facet |
Jens Mayer Christian Harz Laura Sanchez Gavin C. Pereira Esther Maldener Sara R. Heras Lyle W. Ostrow John Ravits Ranjan Batra Eckart Meese Jose Luis García-Pérez John L. Goodier |
author_sort |
Jens Mayer |
title |
Transcriptional profiling of HERV-K(HML-2) in amyotrophic lateral sclerosis and potential implications for expression of HML-2 proteins |
title_short |
Transcriptional profiling of HERV-K(HML-2) in amyotrophic lateral sclerosis and potential implications for expression of HML-2 proteins |
title_full |
Transcriptional profiling of HERV-K(HML-2) in amyotrophic lateral sclerosis and potential implications for expression of HML-2 proteins |
title_fullStr |
Transcriptional profiling of HERV-K(HML-2) in amyotrophic lateral sclerosis and potential implications for expression of HML-2 proteins |
title_full_unstemmed |
Transcriptional profiling of HERV-K(HML-2) in amyotrophic lateral sclerosis and potential implications for expression of HML-2 proteins |
title_sort |
transcriptional profiling of herv-k(hml-2) in amyotrophic lateral sclerosis and potential implications for expression of hml-2 proteins |
publisher |
BMC |
series |
Molecular Neurodegeneration |
issn |
1750-1326 |
publishDate |
2018-08-01 |
description |
Abstract Background Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder. About 90% of ALS cases are without a known genetic cause. The human endogenous retrovirus multi-copy HERV-K(HML-2) group was recently reported to potentially contribute to neurodegeneration and disease pathogenesis in ALS because of transcriptional upregulation and toxic effects of HML-2 Envelope (Env) protein. Env and other proteins are encoded by some transcriptionally active HML-2 loci. However, more detailed information is required regarding which HML-2 loci are transcribed in ALS, which of their proteins are expressed, and differences between the disease and non-disease states. Methods For brain and spinal cord tissue samples from ALS patients and controls, we identified transcribed HML-2 loci by generating and mapping HML-2-specific cDNA sequences. We predicted expression of HML-2 env gene-derived proteins based on the observed cDNA sequences. Furthermore, we determined overall HML-2 transcript levels by RT-qPCR and investigated presence of HML-2 Env protein in ALS and control tissue samples by Western blotting. Results We identified 24 different transcribed HML-2 loci. Some of those loci are transcribed at relatively high levels. However, significant differences in HML-2 loci transcriptional activities were not seen when comparing ALS and controls. Likewise, overall HML-2 transcript levels, as determined by RT-qPCR, were not significantly different between ALS and controls. Indeed, we were unable to detect full-length HML-2 Env protein in ALS and control tissue samples despite reasonable sensitivity. Rather our analyses suggest that a number of HML-2 protein variants other than full-length Env may potentially be expressed in ALS patients. Conclusions Our results expand and refine recent publications on HERV-K(HML-2) and ALS. Some of our results are in conflict with recent findings and call for further specific analyses. Our profiling of HML-2 transcription in ALS opens up the possibility that HML-2 proteins other than canonical full-length Env may have to be considered when studying the role of HML-2 in ALS disease. |
topic |
Amyotrophic lateral sclerosis Human endogenous retrovirus HERV-K(HML-2) Retrotransposon Reverse transcription Provirus |
url |
http://link.springer.com/article/10.1186/s13024-018-0275-3 |
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