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Journal of Virology, June 2002, p. 6147-6154, Vol. 76, No. 12
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.12.6147-6154.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Detection of Viral DNA and Immune Responses to the Human Herpesvirus 6 101-Kilodalton Virion Protein in Patients with Multiple Sclerosis and in Controls

Maria V. Tejada-Simon,1 Ying C. Q. Zang,1 Jian Hong,1 Victor M. Rivera,1 James M. Killian,1 and Jingwu Z. Zhang1,2*

Multiple Sclerosis Research Unit, Department of Neurology and Baylor-Methodist Multiple Sclerosis Center,1 Department of Immunology, Baylor College of Medicine, Houston, Texas 770302

Received 29 October 2001/ Accepted 19 March 2002

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.

* Corresponding author. Mailing address: Department of Neurology, Baylor College of Medicine, 6501 Fannin St., NB302, Houston, TX 77030. Phone: (713) 798-3975. Fax: (713) 798-5665. E-mail: jzang{at}bcm.tmc.edu.

Journal of Virology, June 2002, p. 6147-6154, Vol. 76, No. 12
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.12.6147-6154.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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