On the origin of a pathogenic HERV-W envelope protein present in multiple sclerosis lesions

We read with great interest the recent article by Kremer et al. showing that an envelope (ENV) protein encoded by human endogenous retrovirus type W (HERV-W) is present in myeloid cells in multiple sclerosis (MS) lesions, as detected by mouse monoclonal antibody GN-mAB_03 (3B2H4) directed against HERV-W ENV (1). Furthermore, microglia stimulated with a recombinant HERV-W ENV protein (as encoded by GenBank sequence AF331500) damaged myelinated axons, suggesting that HERV-W ENV may contribute to neurodegeneration in MS, consistent with a recent phase IIb clinical study demonstrating neuroprotective effects of a recombinant anti-HERV-W ENV antibody (GNbAC1) in MS (1). However, despite accumulating evidence for a pathogenic role of HERV-W ENV in MS, the nature of the actual protein is unclear. There are at least 13 HERV-W loci with full-length env genes in the human genome (2), only one of which, in human chromosome 7q21.2, has an uninterrupted open reading frame (ORF) … [↵][1]1To whom correspondence may be addressed. Email: klemens.ruprecht{at}charite.de. [1]: #xref-corresp-1-1