Pathogenesis of the recently identified human herpesviruses 6 and 8

Abstract: Two diseases that for many years have been suspected to be of viral origin are multiple sclerosis (MS) and Kaposi's sarcoma (KS). By the use of a new technique called representational difference analysis both these diseases have recently been associated with new lymphotropic herpesviruses, i.e. human herpesviruses (HHV) 6 and 8. HHV-6 is a ubiquitous virus and a relation to MS has been suggested since the virus has been detected in MS plaques in the brain. The relation between HHV-6 and MS was studied by detection of DNA from herpesviruses I to 7 and studies of the specific immune response to HHV-6 in MS patients and controls. Intrathecal antibody production to HHV-6, but also to EBV and measles virus, was found significantly more often in MS patients compared to controls. Detection of HHV-6 DNA and anti-HHV-6 IgM, IgG subclasses, and lymphoproliferative response did, however, not result in any difference between MS patients and controls. In conclusion none of these analyses gave any support for a major role of HHV-6 in MS pathogenesis. The second part of this thesis concerned HHV-8 seroepidemiology. HHV-8 is believed to be the causative agent of KS, but the role in immuno-competent individuals is uncertain. We developed immunofluorescence assays (IFA) for detection of antibodies to latent and lytic HHV-8 antigens. In Sweden 20% of blood donors were found to have antibodies to HHV-8, and in Eastern Africa (Eritrea) the seroprevalence was 15-45%. Among children 0- 2% were HHV-8 seropositive in Sweden and 7-20% in Eritrea. To assess the accuracy of the IFA, a comparative study involving five laboratories was performed, which showed a poor correlation for all methods except our assay and another IFA. In Tanzanian blood donors, we were able to correlate detection of HHV-8 DNA in serum to the presence of antibodies to both latent and lytic HHV-8 antigen. In Swedish women HHV-8 DNA was not detected in leukocytes or in cervical secretion samples. The finding of HHV-8 DNA in serum an the high seroprevalence in the Eritrean Rashaidas argue for a possible blood borne transmission of HHV-8 in Africa, whereas detection of HHV-8 antibodies in children suggest viral transmission through social contacts. HHV-8 serology still needs further verification, but we believe that detection of antibodies to latent and lytic HHV-8 antigens by IFA is a sensitive assay in investigating chronic infection.