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High frequency of human herpesvirus 6 DNA in multiple sclerosis plaques isolated by laser microdissection
Claudio Cermelli1, Rossana Berti, Samantha S Soldan
1Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
Abstract:
The frequency of human herpesvirus 6 (HHV-6) DNA was assessed in autopsy material from multiple sclerosis (MS) plaques and normal-appearing white matter (NAWM) from brains of persons with MS, healthy brains, and brains of persons with other neurologic diseases. Specific areas from formalin-fixed, paraffin-embedded brain tissue samples were isolated by laser microscope. DNA was extracted from laser microdissected brain material, and HHV-6 genomic sequences were amplified by nested polymerase chain reaction. We analyzed 44 NAWM samples and 64 MS plaques from 13 patients with MS, 46 samples from 13 patients with non-MS neurologic disorders, and 41 samples from 12 healthy control brains. Of the 44 NAWM samples, 7 (15.9%) were positive for HHV-6 DNA sequences, versus 37 (57.8%) of 64 MS plaques (P<.0005). HHV-6 DNA was detected in 10 (21.7%) of 46 samples from patients with non-MS neurologic disorders and in 11 (26.8%) of 41 samples from patients without known neurologic disease. Although the frequency of HHV-6 DNA did not differ significantly by sample type, HHV-6 DNA was significantly more common in MS plaques, suggesting that HHV-6 may play a role in MS pathogenesis.
Insights
Human herpesvirus 6 (HHV-6) DNA was more frequent in multiple sclerosis (MS) plaques than other brain tissues. This suggests HHV-6 may contribute to MS development.
Area of Science:
- Neurovirology
- Neuropathology
- Molecular Biology
Background:
- Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system.
- The role of viral infections, particularly human herpesvirus 6 (HHV-6), in MS pathogenesis remains under investigation.
Purpose of the Study:
- To investigate the presence and frequency of HHV-6 DNA in brain autopsy samples from individuals with MS and control groups.
- To determine if HHV-6 DNA is more prevalent in MS lesions compared to normal-appearing white matter or control brain tissue.
Main Methods:
- Laser microdissection was used to isolate specific brain tissue areas.
- DNA extraction followed by nested polymerase chain reaction (PCR) was employed to detect HHV-6 genomic sequences.
- Samples included MS plaques, normal-appearing white matter (NAWM) from MS patients, non-MS neurological disease controls, and healthy controls.
Main Results:
- HHV-6 DNA was detected in 15.9% of NAWM samples and 57.8% of MS plaques from patients with MS.
- The frequency of HHV-6 DNA in MS plaques was significantly higher than in NAWM (P<.0005).
- HHV-6 DNA detection rates in non-MS neurological disease and healthy control groups were 21.7% and 26.8%, respectively, with no significant difference across sample types overall, except for MS plaques.
Conclusions:
- HHV-6 DNA is significantly more prevalent in multiple sclerosis plaques.
- These findings suggest a potential role for HHV-6 in the pathogenesis of multiple sclerosis.
- Further research is warranted to elucidate the mechanisms by which HHV-6 may contribute to MS.