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


OBJECTIVE
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.
Ablashi
D V
DV
Department of Microbiology, Georgetown University, School of Medicine, Washington, DC, USA. dablashi@abionline.com
Eastman
H B
HB
Owen
C B
CB
Roman
M M
MM
Friedman
J
J
Zabriskie
J B
JB
Peterson
D L
DL
Pearson
G R
GR
Whitman
J E
JE
D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000032:analysis; D002478:Cells, Cultured; D004279:DNA, Viral / Q000032:analysis; D015673:Fatigue Syndrome, Chronic / Q000821:virology*; D006566:Herpesviridae Infections / Q000150:complications* / Q000821:virology; D015654:Herpesvirus 6, Human / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000821:virology; D008213:Lymphocyte Activation; D009103:Multiple Sclerosis / Q000821:virology*; D014775:Virus Activation
D000914:Antibodies, Viral; D000956:Antigens, Viral; D004279:DNA, Viral; D007074:Immunoglobulin G; D007075:Immunoglobulin M