Mayer, JensHarz, ChristianSanchez, LauraPereira, Gavin CMaldener, EstherHeras, Sara ROstrow, Lyle WRavits, JohnBatra, RanjanMeese, EckartGarcía-Pérez, Jose LuisGoodier, John L2023-01-252023-01-252018-08-02http://hdl.handle.net/10668/12788Amyotrophic 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. 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. 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. 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.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Amyotrophic lateral sclerosisEnvelope proteinGag proteinHERV-K(HML-2)Human endogenous retrovirusProvirusRetrotransposonReverse transcriptionAmyotrophic Lateral SclerosisEndogenous RetrovirusesGene Expression ProfilingHumansMembrane ProteinsProvirusesSuperantigensTranscriptomeresearch article30068350open access10.1186/s13024-018-0275-31750-1326PMC6091006https://doi.org/10.1186/s13024-018-0275-3https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6091006/pdf