Pathogenesis of the recently identified human herpesviruses 6 and 8

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.

List of scientific papers

I. Martin C, Enbom M, Soderstrom M, Fredrikson S, Dahl H, Lycke J, Bergstrom T, Linde A. (1997). "Absence of seven human herpesviruses, including HHV-6, by polymerase chain reaction in CSF and blood from patients with multiple sclerosis and optic neuritis. " Acta Neurol Scand 95(5): 280-3
https://pubmed.ncbi.nlm.nih.gov/97332740

II. Enbom M, Martin C, Fredrikson S, Dahl H, Linde A. (1997). "Intrathecal antibody production to lymphotropic herpesviruses in patients with multiple sclerosis and controls." Neurol Infect Epidemiol 2: 107-11

III. Enbom M, Wang FZ, Fredrikson S, Martin C, Dahl H, Linde A. (1999). "Similar humoral and cellular immunological reactivities to human herpesvirus 6 in patients with multiple sclerosis and controls." Clin Diagn Lab Immunol 6(4): 545-9
https://pubmed.ncbi.nlm.nih.gov/99322333

IV. Enbom M, Sheldon J, Lennette E, Schulz T, Ablashi DV, Neipel F, Biberfeld P, Carlberg H, Ljungman P, Nilsson A, Soderstrom T, Wadstrom J, Linde A. (2000). "Antibodies to human herpesvirus 8 latent and lytic antigens in blood donors and potential high-risk groups in sweden: variable frequencies found in a multicenter serological study." J Med Virol 62(4): 498-504
https://pubmed.ncbi.nlm.nih.gov/20528428

V. Enbom M, Tolfvenstam T, Ghebrekidan H, Ruden U, Grandien M, Wahren B, Linde A. (1999). "Seroprevalence of human herpes virus 8 in different Eritrean population groups. " J Clin Virol 14(3): 167-72
https://pubmed.ncbi.nlm.nih.gov/20080516

VI. Enbom M, Strand A, Falk KI, Linde A. (1970). "Detection of EBV, but not HHV-8, DNA in cervical secretions from swedish women." Sex Transm Dis (In Print)

VII. Enbom M, Urassa W, Massambu C, Thorstensson R, Mhalu F, Linde A. (1970). "Detection of human herpesvirus 8 in serum suggests blood borne virus transmission." (Manuscript)