Frequent HHV-6 reactivation in multiple sclerosis (MS) and chronic fatigue syndrome (CFS) patients

• Published in: Journal of clinical virology Vol. 16; no. 3; pp. 179 - 191
• Main Authors: Ablashi, D.V, Eastman, H.B, Owen, C.B, Roman, M.M, Friedman, J, Zabriskie, J.B, Peterson, D.L, Pearson, G.R, Whitman, J.E
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Amsterdam Elsevier B.V 01.05.2000; Elsevier Science
• Subjects: AIDS/HIV; Antibodies, Viral - blood; Antigens, Viral - analysis; Biological and medical sciences; Cells, Cultured; Chronic fatigue syndrome; DNA, Viral - analysis; Fatigue Syndrome, Chronic - virology; Herpesviridae Infections - complications; Herpesviridae Infections - virology; Herpesvirus 6, Human - immunology; Herpesvirus 6, Human - isolation & purification; Herpesvirus 6, Human - physiology; HHV-6; Human herpesvirus 6; Humans; Immunoglobulin G - blood; Immunoglobulin M - blood; Leukocytes, Mononuclear - virology; Lymphocyte Activation; Medical sciences; Multiple sclerosis; Multiple Sclerosis - virology; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Neurology; Virus Activation; Multiple sclerosis; Chronic fatigue syndrome; HHV-6; Human; Nervous system diseases; Reactivation; Pathogenesis; Herpesviridae; Serology; Inflammatory disease; Infection; Virus; Characterization; Herpesvirus hominis 6; Viral disease; Central nervous system disease; Clinical isolate
• ISSN: 1386-6532; 1873-5967
• DOI: 10.1016/S1386-6532(99)00079-7

Background: HHV-6 is a ubiquitous virus and its infection usually occurs in childhood and then becomes a latent infection. HHV-6 reactivation has been shown to play a role in the pathogenesis of AIDS and several other diseases. Objectives: To determine what role HHV-6 infection or reactivation plays in the pathogenesis of multiple sclerosis (MS) and chronic fatigue syndrome (CFS). Results: Twenty-one MS and 35 CFS patients were studied and followed clinically. In these patients, we measured HHV-6 IgG and IgM antibody levels and also analyzed their peripheral blood mononuclear cells (PBMCs) for the presence of HHV-6, using a short term culture assay. In both MS and CFS patients, we found higher levels of HHV-6 IgM antibody and elevated levels of IgG antibody when compared to healthy controls. Seventy percent of the MS patients studied contained IgM antibodies for HHV-6 late antigens (capsid), while only 15% of the healthy donors (HD) and 20% of the patients with other neurological disorders (OND) had HHV-6 IgM antibodies. Higher frequency of IgM antibody was also detected in CFS patients (57.1%) compared to HD (16%). Moreover, 54% of CFS patients exhibited antibody to HHV-6 early protein (p41/38) compared to only 8.0% of the HD. Elevated IgG antibody titers were detected in both the MS and the CFS patients. PBMCs from MS, CFS and HD were analyzed in a short term culture assay in order to detect HHV-6 antigen expressing cells and to characterize the viral isolates obtained as either Variant A or B. Fifty-four percent of MS patients contained HHV-6 early and late antigen producing cells and 87% of HHV-6 isolates were Variant B. Isolates from CFS, patients were predominately Variant A (70%) and isolates from HD were predominately Variant B (67%). Moreover, one isolate from OND was also Variant B. Persistent HHV-6 infection was found in two CFS patients over a period of 2.5 years and HHV-6 specific cellular immune responses were detected in PBMCs from ten CFS patients. Conclusions: In both MS and CFS patients, we found increased levels of HHV-6 antibody and HHV-6 DNA. A decrease in cellular immune responses was also detected in CFS patients. These data suggest that HHV-6 reactivation plays a role in the pathogenesis of these disorders.