Restriction genes for retroviruses influence the risk of multiple sclerosis

PLoS One. 2013 Sep 16;8(9):e74063. doi: 10.1371/journal.pone.0074063. eCollection 2013.

Abstract

We recently described that the autoimmune, central nervous system disease, multiple sclerosis (MS), is genetically associated with the human endogenous retroviral locus, HERV-Fc1, in Scandinavians. A number of dominant human genes encoding factors that restrict retrovirus replication have been known for a long time. Today human restriction genes for retroviruses include amongst others TRIMs, APOBEC3s, BST2 and TREXs. We have therefore looked for a role of these retroviral restriction genes in MS using genetic epidemiology. We here report that markers in two TRIMs, TRIM5 and TRIM22 and a marker in BST2, associated statistically with the risk of getting MS, while markers in or near APOBEC3s and TREXs showed little or no effect. This indicates that the two TRIMs and BST2 influence the risk of disease and thus supports the hypothesis of a viral involvement.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • APOBEC Deaminases
  • Antiviral Restriction Factors
  • Carrier Proteins / genetics
  • Cytidine Deaminase
  • Cytosine Deaminase / genetics
  • Endogenous Retroviruses / genetics
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Minor Histocompatibility Antigens
  • Multiple Sclerosis / genetics*
  • Repressor Proteins / genetics
  • Retroviridae / genetics*
  • Tripartite Motif Proteins
  • Ubiquitin-Protein Ligases

Substances

  • Antiviral Restriction Factors
  • Carrier Proteins
  • Minor Histocompatibility Antigens
  • Repressor Proteins
  • TRIM22 protein, human
  • Tripartite Motif Proteins
  • TRIM5 protein, human
  • Ubiquitin-Protein Ligases
  • Cytosine Deaminase
  • APOBEC Deaminases
  • APOBEC3 proteins, human
  • Cytidine Deaminase

Grants and funding

This work was supported by the Lundbeck Foundation, The Danish Sclerosis Society, and Warwara Larsens Fond. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.