Maria L Elkjaer1, Tobias Frisch2, Arianna Tonazzolli3, Richard Röttger2, Richard Reynolds4, Jan Baumbach5, Zsolt Illes1. 1. Department of Neurology, Odense University Hospital, Odense, Denmark/Neurology Research Unit, Department of Clinical Research, University of Southern Denmark, Odense, Denmark/Neurobiology Research Unit, Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark. 2. Department of Mathematics and Computer Science, University of Southern Denmark, Odense, Denmark. 3. Department of Mathematics and Computer Science, University of Southern Denmark, Odense, Denmark/Department of Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy. 4. Department of Brain Sciences, Faculty of Medicine, Imperial College London, London, UK. 5. TUM School of Life Sciences, Technical University of Munich, Munich, Germany.
Abstract
BACKGROUND: Human endogenous retrovirus (HERV) expression in multiple sclerosis (MS) brain lesions may contribute to chronic inflammation, but expression of genome-wide HERVs in different MS lesions is unknown. OBJECTIVE: We examined the HERV expression landscape in different MS lesions compared to control brains. METHODS: Transcripts from 71 MS brain samples and 25 control WM were obtained by next-generation RNA sequencing and mapped against HERV transcripts across the human genome. Differential expression of mapped HERV-W and HERV-H reads between MS lesion types and controls was analysed. RESULTS: Out of 6.38 billion high-quality paired end reads, 174 million reads (2.73%) mapped to HERV transcripts. There was no difference in HERVs expression level between MS and control brains, but HERV-W transcripts were significantly reduced in chronic active lesions. Of the four HERV-W transcripts exclusively present in MS, ERV3633503 located on chromosome 7q21.13 close to the MS genetic risk locus had the highest number of reads. In the HERV-H family, 75% of transcripts located to nearby 7q21-22 were overrepresented in MS, and ERV3643914 was expressed more than 16 times in MS compared to control brains. CONCLUSION: Novel HERV-W and HERV-H transcripts located at chromosome 7 regions were uniquely expressed in MS lesions, indicating their potential role in brain lesion evolution.
BACKGROUND:Human endogenous retrovirus (HERV) expression in multiple sclerosis (MS) brain lesions may contribute to chronic inflammation, but expression of genome-wide HERVs in different MS lesions is unknown. OBJECTIVE: We examined the HERV expression landscape in different MS lesions compared to control brains. METHODS: Transcripts from 71 MS brain samples and 25 control WM were obtained by next-generation RNA sequencing and mapped against HERV transcripts across the human genome. Differential expression of mapped HERV-W and HERV-H reads between MS lesion types and controls was analysed. RESULTS: Out of 6.38 billion high-quality paired end reads, 174 million reads (2.73%) mapped to HERV transcripts. There was no difference in HERVs expression level between MS and control brains, but HERV-W transcripts were significantly reduced in chronic active lesions. Of the four HERV-W transcripts exclusively present in MS, ERV3633503 located on chromosome 7q21.13 close to the MS genetic risk locus had the highest number of reads. In the HERV-H family, 75% of transcripts located to nearby 7q21-22 were overrepresented in MS, and ERV3643914 was expressed more than 16 times in MS compared to control brains. CONCLUSION: Novel HERV-W and HERV-H transcripts located at chromosome 7 regions were uniquely expressed in MS lesions, indicating their potential role in brain lesion evolution.
Entities:
Keywords:
HERV-H; HERV-W/17; Multiple sclerosis; human brain lesions; human endogenous retroviruses; multiple sclerosis-associated retrovirus; transcriptome
Authors: Silvia Pérez-Pérez; María I Domínguez-Mozo; M Ángel García-Martínez; M Celeste García-Frontini; Noelia Villarrubia; Lucienne Costa-Frossard; Luisa M Villar; Rafael Arroyo; Roberto Álvarez-Lafuente Journal: Front Immunol Date: 2021-11-29 Impact factor: 7.561