Hallett, Rachel Louise; (2001) Molecular epidemiological studies of defined variants of hepatitis B and TT viruses. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

During surveillance of viral hepatitis in England, three particular viral variants, two of hepatitis B virus (HBV) and the other of TT virus (TTV), were identified. Molecular biological and phylogenetic analysis tools, largely developed to study eukaryotic genes, were adapted to define the genetic characteristics of the three variants, to estimate their relative prevalences and to study their relationships with other similar viral strains. The hypothesis investigated in this thesis is that such studies permit the epidemiological and evolutionary significance of particular viral variants to be elucidated. One of the HBV variants, HBVPV, was discovered while analysing clusters of acute hepatitis B infection in northern English prisons. A high throughput assay using denaturing gradient gel electrophoresis (DGGE) was developed to screen HBV PCR products for sequence variation. This approach revealed that while the prevalence of HBVPV was similar in communities in the north and south east of England in 1990, over the next 6 years it dramatically increased in the north, but not the south east. The spread of HBVPV into the community thus appeared to be linked to its prior dissemination among prison inmates. The other HBV variant, HBVAV, was shown by DGGE to infect a large number of patients attending an alternative therapy clinic. Unlike HBVPV, it was not circulating commonly in the community, further implicating it as the cause of the point source outbreak. DNA from the TTV-like variant, PM virus (PMV), was isolated while conducting a search for possible viral causes of acute non-A to E viral hepatitis. The entire PMV genome was characterised and several phylogenetic analysis tools were applied to study the evolutionary and taxonomic relationships between PMV and other TTVs. These approaches permitted clarification of the status of TTVs as viruses that belong to a new genus of the Circoviridae family rather than variants of a single species, and PMV itself as the prototype of a unique species within the genus.

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