Syncytin-1/HERV-W envelope is an early activation marker of leukocytes and is upregulated in multiple sclerosis patients

Eur J Immunol. 2020 May;50(5):685-694. doi: 10.1002/eji.201948423. Epub 2020 Feb 11.


Syncytin-1 is the envelope protein of the human endogenous retrovirus W (HERV-W). It has been related to multiple sclerosis (MS) but its role in cellular immunity and its pathogenic mechanism in the autoimmune context are not fully understood. We analyzed syncytin-1 levels in peripheral blood mononuclear cells (PBMC) subsets from healthy donors, MS patients in relapse or remission, and patients with acute infections by flow cytometry. PBMC cultures were also prepared to analyze protein expression kinetics. MS patients had higher levels of syncytin-1 levels than controls. We found that syncytin-1 is elevated in monocytes during MS relapses and infections. Cells expressing syncytin-1, including monocytes, T and B lymphocytes, and NKs presented mainly an activated phenotype and, upon stimulation with LPS, its levels increased rapidly on antigen-presenting cells. Syncytin-1 ligation promoted the activation of monocytes, as demonstrated by the upregulation of CD80 and the nonclassical subset CD14low CD16+ . Our results suggest an important role for syncytin-1 in the activation of leukocytes. Given that the expression of syncytin-1 is upregulated in MS patients, this protein might be contributing to the autoimmune cascade in the disease.

Keywords: HERV-W; autoimmune disease; leukocytes; multiple sclerosis; syncytin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • B-Lymphocytes / virology
  • B7-1 Antigen / genetics
  • B7-1 Antigen / immunology
  • Case-Control Studies
  • Endogenous Retroviruses / genetics
  • Endogenous Retroviruses / immunology*
  • Female
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / immunology
  • Gene Expression Regulation
  • Gene Products, env / genetics*
  • Gene Products, env / immunology
  • Humans
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / virology
  • Lipopolysaccharide Receptors / genetics
  • Lipopolysaccharide Receptors / immunology
  • Lipopolysaccharides / pharmacology
  • Male
  • Middle Aged
  • Monocytes / drug effects
  • Monocytes / immunology
  • Monocytes / virology*
  • Multiple Sclerosis / genetics*
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / pathology
  • Multiple Sclerosis / virology*
  • Pregnancy Proteins / genetics*
  • Pregnancy Proteins / immunology
  • Primary Cell Culture
  • Receptors, IgG / genetics
  • Receptors, IgG / immunology
  • Recurrence
  • Remission Induction
  • Signal Transduction
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / virology


  • B7-1 Antigen
  • CD14 protein, human
  • CD80 protein, human
  • FCGR3B protein, human
  • GPI-Linked Proteins
  • Gene Products, env
  • Lipopolysaccharide Receptors
  • Lipopolysaccharides
  • Pregnancy Proteins
  • Receptors, IgG
  • syncytin