This thesis describes the genetic analysis of the heterogeneity of HGV/GBV-C and the characterization of the terminal regions of the viral genome. The sequence diversity across the HGV/GBV-C genome was significantly lower than that observed with HCV isolates. Comparative analysis of twenty-seven complete genome HGV/GBV-C sequences indicated the presence of four phylogenetic groups and this study demonstrated that these groupings could be reproduced by analysis of the 5'-untranslated region (5'-UTR) and of various sub-fragments. At the same time, the analysis of the 5'-UTR variability indicated the existence of group-specific polymorphisms, many of which are covariant and consistent with the proposed secondary structure of this region. An important difference between the polyproteins of HGV/GBV-C and HCV is the absence of a putative HGV/GBC-C core protein which is usually encoded at the 5'-end of the genome of flaviviruses. The buoyant density of HGV/GBV-C particles in human plasma was estimated to be between 1.07-1.12 g/ml, much lower than that of the other members of <I>Flaviviridae </I>family, except HCV. No HGV/GBV-C RNA was detected in fractions with densities higher than 1.17 g/ml which is expected for virus particles in immune complexes or in fractions with densities higher than 1.21 g/ml, the density range of HCV nucleocapsids. These biophysical properties correlate with the absence of a core-like protein in the genome of HGV/GBV-C isolates from different phylogenetic groups. The absence of the HGV/GBV-C nucleocapsid was also revealed by the sequence analysis data since no conserved open reading frame capable of encoding a core-like protein was identified. Generally, the untranslated regions at the 5' and 3' termini of a RNA virus genome contain regulatory elements important for viral RNA replication, transcription, translation and viral packaging. A comprehensive comparison and analysis of the primary sequence and secondary structure of the 3'-UTR of different HGV/GBV-C isolates allowed the construction of a common secondary structure model for this region and the identification of structural elements that may be involved in viral replication.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:648987 |
| Date | January 1999 |
| Creators | Cuceanu, Narcisa Manuela |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/22126 |
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