Detection of viral DNA and immune responses to the human herpesvirus 6 101-kilodalton virion protein in patients with multiple sclerosis and in controls.
Human herpesvirus 6 (HHV-6), a latent lymphotropic and neurotropic virus, has been suspected as an etiologic agent in multiple sclerosis (MS). The study was undertaken to correlate virologic evidence for HHV-6 activity with the state of host immunity to HHV-6 in MS patients and control subjects. The study revealed that cell-free DNA of HHV-6 was detected more frequently in both serum and cerebrospinal fluid of MS patients than in those of control subjects. T cells recognizing the recombinant 101-kDa protein (101K) corresponding to the major immunoreactive region unique to HHV-6 occurred at significantly lower precursor frequency in MS patients than in control subjects. The resulting HHV-6-specific T-cell lines obtained from MS patients exhibited skewed cytokine profiles characterized by the inability to produce interleukin-4 (IL-4) and IL-10. The decreased T-cell responses to HHV-6 and the altered cytokine profile were consistent with significantly declined serum immunoglobulin G (IgG) titers for HHV-6 of MS patients compared to those of control subjects. In contrast, elevated serum IgM titers for HHV-6 were detected in the majority of MS patients, which may reflect frequent exposure of B cells to HHV-6. The findings suggest that the decreased immune responses to HHV-6 may be responsible for ineffective clearance of HHV-6 in MS patients.
Tejada-Simon
Maria V
MV
Multiple Sclerosis Research Unit, Department of Neurology and Baylor-Methodist Multiple Sclerosis Center, Baylor College of Medicine, Houston, Texas 77030, USA.
Zang
Ying C Q
YC
Hong
Jian
J
Rivera
Victor M
VM
Killian
James M
JM
Zhang
Jingwu Z
JZ
D000595:Amino Acid Sequence; D000914:Antibodies, Viral / Q000097:blood*; D004279:DNA, Viral / Q000032:analysis* / Q000097:blood / Q000134:cerebrospinal fluid; D006566:Herpesviridae Infections / Q000276:immunology; D015654:Herpesvirus 6, Human / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000276:immunology / Q000821:virology*; D013601:T-Lymphocytes / Q000276:immunology*; D014764:Viral Proteins / Q000737:chemistry / Q000276:immunology*; D014771:Virion / Q000276:immunology
D000914:Antibodies, Viral; D004279:DNA, Viral; D014764:Viral Proteins