The aliens inside us: HERV-W endogenous retroviruses and multiple sclerosis

Mult Scler. 2018 Jan;24(1):42-47. doi: 10.1177/1352458517737370.


Two human endogenous retroviruses of the HERV-W family are proposed as multiple sclerosis (MS) co-factors: MS-associated retrovirus (MSRV) and ERVWE1, whose env proteins showed several potentially neuropathogenic features, in vitro and in animal models. Phase II clinical trials against HERV-Wenv are ongoing. HERV-W/MSRV was repeatedly found in MS patients, in striking parallel with MS stages, active/remission phases, and therapy outcome. The HERV-Wenv protein is highly expressed in active MS plaques. Early MSRV presence in spinal fluids predicted worst MS progression 10 years in advance. Effective anti-MS therapies strongly reduced MSRV/Syncytin-1/HERV-W expression. The Epstein-Barr virus (EBV) activates HERV-W/MSRV in vitro and in vivo, in patients with infectious mononucleosis and controls with high anti-EBNA1-IgG titers. Thus, the two main EBV/MS links (infectious mononucleosis and high anti-EBNA1-IgG titers) are paralleled by activation of HERV-W/MSRV. It is hypothesized that EBV may act as initial trigger of future MS, years later, by activating MSRV, which would act as direct neuropathogenic effector, before and during MS.

Keywords: HERV-W/MSRV/Syncytin-1 human endogenous retroviruses; MS pathogenesis; MS therapy; biomarker; dual virus hypothesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Endogenous Retroviruses*
  • Epstein-Barr Virus Infections*
  • Herpesvirus 4, Human
  • Humans
  • Multiple Sclerosis / virology*