Human herpesvirus 6 in multiple sclerosis and encephalitis

Human herpesvirus 6 (HHV-6) was identified from patients with HIV and lymphoproliferative diseases in 1986. It is a β-herpesvirus and is divided into two subgroups, variants A and B. HHV-6 variant B is the cause of exanthema subitum, while variant A has not yet definitely proven to cause any disease. HHV-6, especially variant A, is a highly neurotropic virus and has been associated with many diseases of the central nervous system (CNS) such as encephalitis and multiple sclerosis (MS). The present studies were aimed to elucidate the role of HHV-6 and its two variants in neurological infections. Special attention was given to study the possible role of HHV-6 in the pathogenesis of MS. We studied the expression of HHV-6 antigens using immunohistochemistry in brain autopsy samples from patients with MS and controls. HHV-6 antigen was identified in 70% of MS specimens whereas 30% of control specimens expressed HHV-6 antigen. In addition, HHV-6 antigen was associated with elevated expression of tissue plasminogen activator (tPA), an enzyme taking part in both neuronal development and degeneration. In order to study the role of HHV-6 in MS further, serum and cerebrospinal fluid (CSF) samples were collected from patients with MS and patients with other neurological diseases (OND) from patients visiting Helsinki University Central Hospital Neurological Outpatient Clinic during the years 2003 and 2004. A total of 27 patients with clinically definite MS (CDMS) and 19 patients with clinically possible MS (CPMS) and ageand gendermatched control patients with OND were included. In addition, we studied 53 children with suspected encephalitis. Samples were consecutively collected from the first and last quarter of the year 1995, from the sample series sent to the Department of Virology, University of Helsinki, for suspected viral encephalitis. We developed an immunofluorescence IgG-avidity assay for the detection of primary HHV6A and HHV-6B infection. For HHV-6B antibodies, no differences were observed between patients with MS and OND.