title: No serological evidence for a role of HHV-6 infection in chronic fatigue syndrome.
abstract: Human herpesvirus 6A (HHV-6A) and human herpesvirus 6B (HHV-6B) are associated with a variety of conditions including rash, fever, and encephalitis and may play a role in several neurological diseases. Here luciferase immunoprecipitation systems (LIPS) was used to develop HHV-6 serologic diagnostic tests using antigens encoded by the U11 gene from HHV-6A (p100) and HHV-6B (p101). Analysis of the antibody responses against Renilla luciferase fusions with different HHV-6B p101 fragments identified an antigenic fragment (amino acids 389 to 858) that demonstrated ~86% seropositivity in serum samples from healthy US blood donors. Additional experiments detected a HHV-6A antigenic fragment (amino acids 751-870) that showed ~48% antibody seropositivity in samples from Mali, Africa, a known HHV-6A endemic region. In contrast to the high levels of HHV-6A immunoreactivity seen in the African samples, testing of US blood donors with the HHV-6A p100 antigenic fragment revealed little immunoreactivity. To potentially explore the role of HHV-6 infection in human disease, a blinded cohort of controls (n=59) and chronic fatigue syndrome (CFS) patients (n=72) from the US was examined for serum antibodies. While only a few of the controls and CFS patients showed high level immunoreactivity with HHV-6A, a majority of both the controls and CFS patients showed significant immunoreactivity with HHV-6B. However, no statistically significant differences in antibody levels or frequency of HHV-6A or HHV-6B infection were detected between the controls and CFS patients. These findings highlight the utility of LIPS for exploring the seroepidemiology of HHV-6A and HHV-6B infection, but suggest that these viruses are unlikely to play a role in the pathogenesis of CFS.
authors.affiliation: Neurobiology and Pain Therapeutics Section, Laboratory of Sensory Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health Bethesda, MD.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Burbelo
authors.forename: Ahmad
authors.initials: A
authors.lastname: Bayat
authors.forename: Jason
authors.initials: J
authors.lastname: Wagner
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Nutman
authors.forename: James N
authors.initials: JN
authors.lastname: Baraniuk
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Iadarola
keywords: Chronic Fatigue Syndrome (CFS); Human Herpes Virus-6 (HHV6); luciferase immunoprecipitation systems (LIPS)