title: Serological and virological investigation of the role of the herpesviruses EBV, CMV and HHV-6 in post-infective fatigue syndrome.
abstract: Multiple previous studies have sought evidence for ongoing, active infection with, or reactivation of, Herpesviruses in patients with chronic fatigue syndrome (CFS), with conflicting results. This study aimed to clarify this by studying 20 patients enrolled in a well-characterized model of the onset and evolution of CFS, the prospective cohort of the Dubbo Infection Outcomes Study (DIOS). The patients selected for examination included five CFS patients with primary Epstein-Barr virus (EBV) infection; five CFS patients with acute viral infection not caused by EBV; and 10 matched controls with prompt resolution of primary EBV infection. Serum samples from three timepoints were assayed using a comprehensive range of serological assays for EBV, HHV-6, and CMV. Viral genomes were assessed using quantitative PCR assays. All patients were seropositive for HHV-6, and 10 were seropositive for CMV at infection baseline (five patients and five controls). Low titer CMV IgM antibodies were found at infection baseline in two of these cases and three control patients. HHV-6 IgG antibody titers were highest at infection baseline but did not differ between the CFS cases and the control patients. There were increases in EBV IgG VCA p18, EBNA-1 IgG, and EA IgG titers over time, but these did not differ between CFS cases and control patients. EBV and HHV6 DNA levels were at control levels in a minority of samples, and CMV was undetectable in all samples. These data do not support the hypothesis of ongoing or reactivated EBV, HHV-6, or CMV infection in the pathogenesis of CFS.
authors.affiliation: Center for Infection and Inflammation Research, School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia. b.cameron@unsw.edu.au
authors.forename: Barbara
authors.initials: B
authors.lastname: Cameron
authors.forename: Louis
authors.initials: L
authors.lastname: Flamand
authors.forename: Hedy
authors.initials: H
authors.lastname: Juwana
authors.forename: Jaap
authors.initials: J
authors.lastname: Middeldorp
authors.forename: Zin
authors.initials: Z
authors.lastname: Naing
authors.forename: William
authors.initials: W
authors.lastname: Rawlinson
authors.forename: Dharam
authors.initials: D
authors.lastname: Ablashi
authors.forename: Andrew
authors.initials: A
authors.lastname: Lloyd
mesh_terms: D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D015673:Fatigue Syndrome, Chronic / Q000821:virology*; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D015654:Herpesvirus 6, Human / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D006801:Humans; D007124:Immunoenzyme Techniques; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D004279:DNA, Viral; D007074:Immunoglobulin G