Unbiased examination of genome-wide human endogenous retrovirus transcripts in MS brain lesions.

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.