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Gene expression studies of lytic infection and chromosomal integration of human herpesvirus 6

Human herpesvirus 6 (HHV-6) was discovered in 1986 in patients with lymphoproliferative diseases and it has a predominant tropism for CD4+ T cells in vitro and in vivo. The virus can be divided into two variants: HHV-6A and 6B, based on the differences in biological properties and DNA sequences. HHV-6B has been shown to be the causative agent of exanthem subitum while HHV-6A has no clear association with any disease yet. The genome for both variants has been defined and each encodes just over 100 open readings frames (ORFs). However, there is limited knowledge regarding the functions and transcription kinetics of most ORFs. This thesis discusses the development of DNA microarrays for HHV-6 and the application of the arrays to characterise HHV-6B gene expression in the SupT1 cell line. The expression pattern of individual viral genes over a 60h time course (<1 replication cycle) was profiled. Viral genes were further classified into three kinetic groups: immediately-early (IE), early (E), and late (L), according to their transcriptional activity in the absence of de novo protein synthesis or DNA replication. In addition, HHV-6 presents an atypical stage in the herpesvirus life cycle in which the viral genome is integrated into host chromosomes. The prevalence of HHV-6 integration was estimated to be between 0.21% to 3%. An individual harbouring integrated HHV-6 was previously identified. The molecular biology and gene expression of this integrated HHV-6 DNA were characterised. Expression of viral genes belonging to all three kinetic classes (IE, E, and L) was detected in vitro and ex vivo. The data strongly suggest that the chromosomal HHV-6 sequence is transcriptionally active and the implications of this are discussed.
Date January 2008
CreatorsTsao, E. H. F.
PublisherUniversity College London (University of London)
Source SetsEthos UK
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation

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