Figure 1.

Putative mechanisms of human endogenous retrovirus (HERV)‐related autoimmunity in multiple sclerosis. (A) HERV‐encoded RNAs with intact open reading frames (ORFs) can be translated into proteins. Some of these (eg HERV‐K, HCML‐ARV) are in close proximity to SNPs shown to be associated with MS in genomewide association studies and representing genes involved in immune responses and vitamin D metabolism. (B) Some HERV proteins, notably MASP‐3, HERV‐H and HERV‐W, are expressed on the surface of normal cells including B cells. This serological response may be associated with autoimmunity, although causality has yet to be established. (C) HERVs are integral to the human genome but are epigenetically inactivated under normal conditions. HERV expression may be induced by environmental triggers including HSV‐1, HHV‐6, VZV and EBV viruses to stimulate an immune response and autoimmunity. (D) The MRSV‐Env protein has been identified in MS plaques and is brain selective and immunopathogenic so may directly stimulate an autoimmune response.1 Furthermore, this protein inhibits differentiation of oligodendrocyte precursors so may have a negative feedback effect in the brains of patients with MS 2