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Transcriptional profiling of HERV-K(HML-2) in amyotrophic lateral sclerosis and potential implications for expression of HML-2 proteins

Research output: Contribution to journalArticle

  • 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 Garcia-Perez
  • John L. Goodier

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Original languageEnglish
Article number39
Number of pages25
JournalMolecular Neurodegeneration
Publication statusPublished - 2 Aug 2018


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.

    Research areas

  • Amyotrophic lateral sclerosis, Human endogenous retrovirus, HERV-K(HML-2), Retrotransposon, Reverse transcription, Provirus, Envelope protein, Gag protein, ENDOGENOUS RETROVIRUS-K, ZINC-FINGER PROTEIN, EMBRYONIC STEM-CELLS, HERV-K, REVERSE-TRANSCRIPTASE, DNA METHYLATION, ANDROGEN RECEPTOR, HUMAN TISSUES, REC PROTEIN, NP9

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