Co-localization of human herpes virus 6 and tissue plasminogen activator in multiple sclerosis brain tissue.
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.


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.
Virtanen
Jussi Oskari
JO
Haartman Institute, Department of Virology, University of Helsinki, Finland.
Zabriskie
John B
JB
Sirén
Vappu
V
Friedman
Jacqueline E
JE
Lyons
Michael J
MJ
Edgar
Mark
M
Vaheri
Antti
A
Koskiniemi
Marjaleena
M
D000956:Antigens, Viral / Q000276:immunology; D001921:Brain / Q000821:virology*; D016022:Case-Control Studies; D015654:Herpesvirus 6, Human / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000821:virology*; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
D000956:Antigens, Viral; D010959:Tissue Plasminogen Activator