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Updated: Aug 19, 2026

Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Co-localization of human herpes virus 6 and tissue plasminogen activator in multiple sclerosis brain tissue
Jussi Oskari Virtanen1, John B Zabriskie, Vappu Sirén
1Haartman Institute, Department of Virology, University of Helsinki, Finland.
Background:
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system of unknown etiology. Several viruses have been suggested as playing a role in the pathogenesis of MS. The aim of this study was to investigate the interrelationship of human herpesvirus 6 (HHV-6) and plasminogen activation at the cellular level in MS plaques.
Material/Methods:
Brain tissue specimens obtained from autopsies of 15 patients with MS and 10 controls were studied immunohistochemically for HHV-6 and cytomegalovirus (CMV) antigen and tissue plasminogen activator (tPA) protein. The presence of Ebstein-Barr virus (EBV) EBER RNA was studied using RNA in situ hybridization.
Results:
HHV-6 antigen was identified in the cells of 67% (10/15) of MS brain sections and 30% (3/10) of the control sections. All samples were negative for CMV antigen and all samples with intact RNA were negative for EBV EBER RNA as demonstrated by in situ hybridization. tPA expression was found to be increased in MS plaques compared with the control samples. Interestingly, in 5 MS samples both HHV-6 antigen and tPA stained clearly, compared with none in the controls, but HHV-6 and tPA only occasionally co-localized in the same cells.
Conclusions:
At the cellular level, HHV-6 and plasminogen activation seem to co-localize in MS.
Insights
Human herpesvirus 6 (HHV-6) and plasminogen activation, a key process in inflammation, appear together in multiple sclerosis (MS) brain lesions. This suggests a potential link between HHV-6 infection and MS pathogenesis.
Area of Science:
- Neuroimmunology
- Virology
- Pathology
Background:
- Multiple sclerosis (MS) is a chronic central nervous system inflammatory disease with unknown causes.
- Viruses, including human herpesvirus 6 (HHV-6), are investigated for their potential role in MS development.
- Understanding the interplay between viral infections and inflammatory processes in MS is crucial.
Purpose of the Study:
- To investigate the relationship between human herpesvirus 6 (HHV-6) and plasminogen activation within MS lesions.
- To examine the cellular co-localization of HHV-6 and tissue plasminogen activator (tPA) in the brains of MS patients.
Main Methods:
- Immunohistochemistry was used to detect HHV-6, cytomegalovirus (CMV) antigens, and tPA protein in brain tissue from 15 MS patients and 10 controls.
- RNA in situ hybridization was employed to identify Epstein-Barr virus (EBV) EBER RNA.
Main Results:
- HHV-6 antigen was detected in 67% of MS brain sections, compared to 30% in controls.
- Tissue plasminogen activator (tPA) expression was elevated in MS plaques.
- While HHV-6 and tPA were found together in some MS samples, they rarely co-localized within the same cells.
Conclusions:
- HHV-6 and plasminogen activation show evidence of co-localization at the cellular level in multiple sclerosis.
- These findings suggest a potential link between HHV-6 infection and the inflammatory environment of MS plaques.

