Activation of MSRV-type endogenous retroviruses during infectious mononucleosis and Epstein-Barr virus latency: the

Giuseppe Mameli1, Giordano Madeddu, Alessandra Mei

  • 1Department of Biomedical Sciences, University of Sassari, Sassari, Italy.

Plos One
|November 16, 2013
PubMed

Insights

Epstein Barr virus (EBV) infection, particularly infectious mononucleosis (IM), correlates with Human Endogenous Retrovirus W (HERV-W) activation. This activation may be the missing link connecting EBV to multiple sclerosis (MS) pathogenesis.

Area of Science:

  • Neuroimmunology
  • Virology
  • Genetics

Background:

  • The etiology of multiple sclerosis (MS) remains unclear, with environmental factors and genetic predisposition implicated.
  • Epstein Barr virus (EBV) and Human Endogenous Retroviruses (HERV-W) are proposed co-factors in MS pathogenesis.
  • Previous research noted links between EBV infection (infectious mononucleosis, IM) and high anti-EBNA IgG titers with MS, alongside continuous HERV-W expression in MS patients.

Purpose of the Study:

  • To investigate in vivo activation of HERV-W/MSRV in young adults with infectious mononucleosis (IM) symptoms.
  • To determine the correlation between EBV infection status and HERV-W/MSRV activation.
  • To explore the potential role of HERV-W/MSRV activation as a link between EBV and MS.

Main Methods:

  • Analysis of HERV-W/MSRV transcripts and proteins in blood mononuclear cells of IM patients and healthy controls.
  • Stratification of healthy controls based on EBV infection status (EBV-negative, latent EBV infection with varying anti-EBNA-1 IgG titers).
  • Flow cytometry to assess cell surface HERV-Wenv protein expression.

Main Results:

  • Significant activation of HERV-W/MSRV was observed in IM patients, with a 2Log10 increase in MSRV-type env mRNA.
  • A direct correlation between prior EBV infection (indicated by anti-EBNA-1 IgG titers) and MSRV mRNA accumulation was found in healthy controls.
  • Increased percentages of cells expressing surface HERV-Wenv protein were detected in IM patients and individuals with past EBV infection.

Conclusions:

  • HERV-W/MSRV activation occurs in vivo during infectious mononucleosis and correlates with EBV infection history.
  • These findings suggest HERV-W/MSRV activation serves as a potential link between EBV and the development of multiple sclerosis.
  • The study opens new avenues for therapeutic interventions targeting HERV-W in MS.

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