Di Alberti, Luca; (1998) Human herpesvirus 8 and new pathological associations. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The prevalence, diversity and disease association of human herpesvirus 8 (HHV-8) may be more extensive than previously reported. HHV-8 subgenomic sequences in tissues representing a broad range of pathologies were investigated. DNA from the KS330₂₃₃ region of open reading frame (ORF) 26 in various oral lesions in HIV-infected and HIV-seronegative individuals was first sought. HHV-8 DNA sequences were amplified in 12 out of 16 of non-KS oral lesions of HIV-positive but none of the HIV-negative controls. A diversity of sequences was observed. The presence of HHV-8 DNA in two groups of granulomatous diseases—sarcoidosis and oral granulomatous disorders—was then investigated. Thirty-eight out of 39 (97.4%) sarcoid tissues and all 17 oral granulomatous tissues were positive for HHV-8 DNA in ORFs25 and 26. A diversity of ORF26 sequences was again observed. ORF26 sequences from tissues of the granulomatous disorders and from a range of non-granulomatous diseases (Kaposi's sarcoma, B-cell lymphoma, Kikuchi's disease and other lymphadenitides) were compared with sequences reported by other laboratories. The sequences could be categorised into at least 8 groups based on hot-spot mutations in codons 134, 141, 152, 167 and 169 of the ORF26 protein. Intra-host variability of HHV-8 was then investigated in a selection of neoplastic and non-neoplastic tissues. Wide intra-host and intra-lesional hypervariability were found, particularly in patients with sarcoidosis and Kikuchi's disease. Two mechanisms for genotyping such a wide range of variability were postulated: existence of HHV-8 as quasispecies and co-infection by multiple HHV-8 variants. It is concluded that: 1. HHV-8 DNA ORF26 is commonly found in oral lesions of HIV-infected patients, in sarcoid tissues and in oral granulomatous tissues; 2. the virus may be classified into at least eight genetic groups based on sequence variations in ORF26; and 3. the inter-host, intra-host and intra-lesional sequence variability of ORF26 can be considerable.

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