New Insights into Endogenous Retrovirus-K Transcripts in Amyotrophic Lateral Sclerosis

Moreno-Martinez, L.; Macías-Redondo, S.; Strunk, M.; Guillén-Antonini, M.I.; Lunetta, C.; Tarlarini, C.; Penco, S.; Calvo, A.C.; Osta, R.; Schoorlemmer, J. New Insights into Endogenous Retrovirus-K Transcripts in Amyotrophic Lateral Sclerosis. Int. J. Mol. Sci. 2024, 25, 1549.

Retroviral reverse transcriptase activity and the increased expression of human endogenous retroviruses (HERVs) are associated with amyotrophic lateral sclerosis (ALS). We were interested in confirming HERVK overexpression in the ALS brain, its use as an accessory diagnostic marker for ALS, and its potential interplay with neuroinflammation. Using qPCR to analyze HERVK expression in peripheral blood mononuclear cells (PBMCs) and in postmortem brain samples from ALS patients, no significant differences were observed between patients and control subjects. By contrast, we report alterations in the expression patterns of specific HERVK copies, especially in the brainstem. Out of 27 HERVK copies sampled, the relative expression of 17 loci was >1.2-fold changed in samples from ALS patients. In particular, the relative expression of two HERVK copies (Chr3-3 and Chr3-5) was significantly different in brainstem samples from ALS patients compared with controls. Further qPCR analysis of inflammation markers in brain samples revealed a significant increase in NLRP3 levels, while TNFA, IL6, and GZMB showed slight decreases. We cannot confirm global HERVK overexpression in ALS, but we can report the ALS-specific overexpression of selected HERVK copies in the ALS brain. Our data are compatible with the requirement for better patient stratification and support the potential importance of particular HERVK copies in ALS.