Cytomegalovirus, Epstein-Barr virus, and human herpesvirus-6 infections in patients with myalgic еncephalomyelitis/chronic fatigue syndrome

J Med Virol. 2020 Dec;92(12):3682-3688. doi: 10.1002/jmv.25744. Epub 2020 Mar 11.


Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling multisystem chronic disease. The etiology and pathogenesis of ME/CFS are unknown. Infections of cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human herpesvirus-6 (HHV-6) are suspected as etiological agents for ME/CFS. This study aims to estimate prevalence and type (active/latent) of EBV, CMV, and HHV-6 infections in Bulgarian ME/CFS patients. In the study were included 58 patients with ME/CFS and 50 healthy controls. Virus-specific antibodies were detected by enzyme-linked immunosorbent assay and viral genomic sequences in peripheral blood mononuclear cell (PBMCs) and plasma samples by nested polymerase chain reaction (PCR). We did not observe any significant differences in virus-specific immunoglobulin G and immunoglobulin M positivity rates between patients with ME/CFS and control group. In ME/CFS plasma samples, EBV DNA was found in 24.1%, CMV DNA in 3.4%, and HHV-6 DNA in 1.7% of samples. EBV DNA was detected in 4%, and CMV and HHV-6 DNA were not found in plasma samples of controls. The frequency of viral genome detection in PBMCs of patients and controls was 74% vs 78% for CMV, 81% vs 84% for EBV, and 82.8% vs 82% for HHV-6. The difference in frequency of EBV active infection in ME/CFS and control group was statistically significant (P = .0027). No ME/CFS and control individuals with active CMV and HHV-6 infection were observed. In conclusion, this study using both serological and PCR-based techniques for distinguishing between active and latent infection showed high rate of active EBV infection among patients with ME/CFS indicating that at least in a subset of cases, EBV is important factor for the development of disease.

Keywords: CMV; EBV; ELISA; HHV-6 infection; PCR; active infection; myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Viral* / blood
  • Cytomegalovirus Infections* / complications
  • Cytomegalovirus Infections* / epidemiology
  • Cytomegalovirus Infections* / virology
  • Cytomegalovirus* / genetics
  • Cytomegalovirus* / immunology
  • Cytomegalovirus* / isolation & purification
  • DNA, Viral* / blood
  • DNA, Viral* / genetics
  • Enzyme-Linked Immunosorbent Assay
  • Epstein-Barr Virus Infections* / complications
  • Epstein-Barr Virus Infections* / epidemiology
  • Epstein-Barr Virus Infections* / virology
  • Fatigue Syndrome, Chronic* / virology
  • Female
  • Herpesvirus 4, Human* / genetics
  • Herpesvirus 4, Human* / immunology
  • Herpesvirus 4, Human* / isolation & purification
  • Herpesvirus 6, Human* / genetics
  • Herpesvirus 6, Human* / isolation & purification
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin M / blood
  • Leukocytes, Mononuclear / virology
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Prevalence
  • Roseolovirus Infections / complications
  • Roseolovirus Infections / epidemiology
  • Roseolovirus Infections / virology
  • Young Adult


  • Antibodies, Viral
  • DNA, Viral
  • Immunoglobulin G
  • Immunoglobulin M