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Human herpesvirus 6 genome and antigen in acute multiple sclerosis lesions
Andrew D Goodman1, David J Mock, James M Powers
1Department of Neurology, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA. andrew_goodman@urmc.rochester.edu
Abstract:
Evidence for a candidate multiple sclerosis (MS) virus, human herpesvirus 6 (HHV-6), was sought in biopsy specimens of acute lesions that presented clinically as cerebral tumors obtained from 5 patients. Histopathology, magnetic resonance imaging, and clinical course confirmed the diagnosis of MS in each case. A sensitive in situ polymerase chain reaction (ISPCR) method was used to detect HHV-6 genome, in conjunction with immunocytochemical staining (ICC) to detect viral and cellular antigens. ISPCR revealed numerous oligodendrocytes, lymphocytes, and microglia containing HHV-6 genome within all lesions, whereas ICC showed only the HHV-6 glycoprotein 116 antigen in some reactive astrocytes and microglia. High frequencies of neuroglial and inflammatory cells containing HHV-6 genome were present in acute-phase lesion tissue from patients who were free of the effects of chronic MS and had not been received immunomodulatory therapy for MS. The prevalence of HHV-6 genome-containing cells, including oligodendrocytes, in each lesion suggests that HHV-6 plays a role in the demyelinative pathogenesis of MS; the significance of the discrepant expression of viral antigens remains uncertain.
Insights
Human herpesvirus 6 (HHV-6) DNA was found in brain lesions of multiple sclerosis (MS) patients. This suggests HHV-6 may play a role in MS disease development and demyelination.
Area of Science:
- Neurovirology
- Immunology
Background:
- Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system.
- The etiology of MS remains largely unknown, with viral infections being a suspected contributing factor.
Observation:
- Biopsy specimens from acute MS lesions clinically resembling cerebral tumors were analyzed.
- A sensitive in situ polymerase chain reaction (ISPCR) method was employed to detect human herpesvirus 6 (HHV-6) genome.
Findings:
- HHV-6 genome was detected in oligodendrocytes, lymphocytes, and microglia within all analyzed MS lesions.
- Immunocytochemical staining revealed HHV-6 glycoprotein 116 antigen in some reactive astrocytes and microglia.
- High frequencies of HHV-6 genome-containing cells were found in acute lesions from untreated patients.
Implications:
- The presence of HHV-6 genome in various neural and inflammatory cells suggests a potential role for HHV-6 in the demyelinating pathogenesis of MS.
- Further research is needed to understand the discrepant viral antigen expression and the precise mechanism of HHV-6 involvement in MS.