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.
Department of Mathematics and Computer Science, University of Southern Denmark, Odense, Denmark.
Mult Scler. 2021 Oct;27(12):1829-1837. doi: 10.1177/1352458520987269. Epub 2021 Jan 19.
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.
We examined the HERV expression landscape in different MS lesions compared to control brains.
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.
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.
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.
人类内源性逆转录病毒（HERV）在多发性硬化症（MS）脑损伤中的表达可能导致慢性炎症，但不同 MS 损伤中全基因组 HERV 的表达情况尚不清楚。
我们比较了不同 MS 病变与对照脑之间的 HERV 表达谱。
通过下一代 RNA 测序获得 71 个 MS 脑样本和 25 个对照 WM 的转录本，并将其映射到人类基因组中的 HERV 转录本上。分析了 MS 病变类型与对照之间映射的 HERV-W 和 HERV-H 读数的差异表达。
在 63.8 亿个高质量的配对末端读数中，有 1.74 亿个读数（2.73%）映射到 HERV 转录本。MS 和对照脑之间的 HERV 表达水平没有差异，但慢性活动病变中 HERV-W 转录本显著减少。在仅存在于 MS 中的四个 HERV-W 转录本中，位于染色体 7q21.13 上靠近 MS 遗传风险位点的 ERV3633503 具有最高的读数数。在 HERV-H 家族中，位于 7q21-22 附近的 75%的转录本在 MS 中过度表达，与对照脑相比，ERV3643914 在 MS 中的表达增加了 16 倍以上。
位于 7 号染色体区域的新型 HERV-W 和 HERV-H 转录本在 MS 病变中特异性表达，表明它们在脑损伤演变中的潜在作用。
