Association of Active Human Herpesvirus-6, -7 and Parvovirus B19 Infection with Clinical Outcomes in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract

Frequency of active human herpesvirus-6, -7 (HHV-6, HHV-7) and parvovirus B19 (B19) infection/coinfection and its association with clinical course of ME/CFS was evaluated. 108 ME/CFS patients and 90 practically healthy persons were enrolled in the study. Viral genomic sequences were detected by PCR, virus-specific antibodies and cytokine levels—by ELISA, HHV-6 variants—by restriction analysis. Active viral infection including concurrent infection was found in 64.8% (70/108) of patients and in 13.3% (12/90) of practically healthy persons. Increase in peripheral blood leukocyte DNA HHV-6 load as well as in proinflammatory cytokines' levels was detected in patients during active viral infection. Definite relationship was observed between active betaherpesvirus infection and subfebrility, lymphadenopathy and malaise after exertion, and between active B19 infection and multijoint pain. Neuropsychological disturbances were detected in all patients. The manifestation of symptoms was of more frequent occurrence in patients with concurrent infection. The high rate of active HHV-6, HHV-7 and B19 infection/coinfection with the simultaneous increase in plasma proinflammatory cytokines' level as well as the association between active viral infection and distinctive types of clinical symptoms shows necessity of simultaneous study of these viral infections for identification of possible subsets of ME/CFS.

The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability

“…Reactivation of HHV6, even in immunocompetent individuals, leads to dysregulation within signaling pathways governing the innate immune response, and increased levels of neuropathology [96]. The specificity and sensitivity of recent serology assays for the presence of IgG and IgM antibodies to HHV6 in the blood compartment are high [102], and the presence of HHV6 can readily be detected by nested polymerase chain reaction (PCR) following culture of peripheral mononuclear blood cells extracted from an infected patient. The most recent assays can discriminate between DNA from actively replicating HHV6A and that from chromosomally integrated virus [103].…”

“…There is also evidence that functional polymorphisms in the genes coding for IFNγ and transforming growth factor β1 (TGF-β1) are associated with a greater likelihood of developing symptoms following Parvovirus B19 infection [113]. Current serology assays have a high sensitivity and specificity to the presence of the VP2 structural protein of parvovirus in blood compartments [102]. In similar vein, B19 DNA can readily be detected by PCR following culture of PMBCs extracted from infected people [103].…”

“…In similar vein, B19 DNA can readily be detected by PCR following culture of PMBCs extracted from infected people [103]. However, there is a caveat, as B19 DNA can be detected in tissue by PCR, when examination of any blood compartment is negative [102].…”

T. Egeland og medarbeidere svarer:

“…Flere studier har undersøkt hvorvidt pasienter med CFS/ME har kroniske infeksjoner, men foreløpig er det ikke entydige svar (51)(52)(53) . Vedvarende autonom dysregulering kan også vaere med på å opprettholde tilstanden (31) .…”

Chronic fatigue syndrome: the current status and future potentials of emerging biomarkers

“…69 One group found increased active rates of infection by Human Herpesvirus 6, (HHV-6), Human Herpesvirus 7 (HHV-7), and parvovirus B19 in patients with CFS when compared to controls. 70 One study found that 94% of patients with CFS had decreased circulating B-cells with a depletion of peripheral blood CD19+IgM+ mature B-lymphocytes, noting another possible connection between EBV and abnormal immune responses. While etiology is not yet well established, there remains potential for virus-specific antibodies to help delineate possible subtypes of CFS in the future.…”