Thesis (Ph. D.)--University of Hong Kong, 2009. / Includes bibliographical references (leaves 174-194). Also available in print.

published_or_final_version / Microbiology / Doctoral / Doctor of Philosophy

No description available.

The viral dynamics of the hepatitis C virus (HCV) in newly acquired infection are not well understood. HCV exists within an individual as a spectrum of minor variants termed quasispecies. The evolution of minor variants may contribute to viral escape of the host?s immune response, thereby facilitating development of chronic infection. The hypervariable 1 region (HVR1) is the most heterogeneous part of the HCV genome and contains a putative B-cell epitope. Thus, diversity in HVR1 could be a strategy used to evade neutralising antibodies. Acutely infected individuals (n=24) were examined with the aim of defining HVR1 quasispecies diversity in acute infection. The characterisation of the E1/HVR1 sequence and host specific evolution of HCV minor variants in treatment nonresponders was also investigated. HCV E1/HVR1 fragments were amplified from 48 sera using a combined reverse transcription-polymerase chain reaction (RT-PCR). Products were TA cloned into pCRIITOPO and approximately 10-20 clones were sequenced from each sample. HVR1 quasispecies diversity was examined longitudinally via sequence analysis. Quasispecies diversity was characterised primarily by mean nucleotide diversity. The mean HVR1 diversity of the acute cohort (n=48; 2.12% ?? 2.22) was lower than the diversity obtained for a cohort of chronically infected individuals (n=99; 4.5% ?? 5.1). There was no significant difference in mean HVR1 diversity between the HIV/HCV co-infected and HCV mono-infected groups (p=0.99) or between the clearer and non-clearer groups (p=0.85). Examination of amino acid usage and the hydropathic profile of each position in HVR1 revealed that sequence variation was confined to specific sites. The investigation of host specific evolution of HVR1 quasispecies demonstrated that minor variants (comprising 10- 20% of a population) became the dominant species over time in two treatment non-responders. These variants bore mutations that were not reflected in the consensus sequence of their respective populations at the initial timepoint analysed. Common infection was identified by 98% HVR1 sequence homology within two pairs of individuals. The evolution of common strains appeared to be different between individuals, suggesting host pressures may influence quasispecies evolution. This thesis provided an insight into the viral dynamics and host specific evolution of acute phase quasispecies.

Primary Epstein-Barr virus (EBV) infection in childhood is typically asymptomatic, but infection later in life results in a mononucleosis with the illness severity ranging from asymptomatic to requiring hospitalisation. The illness is generally short-lived (four to six weeks following onset of symptoms), but persistent disabling symptoms (lasting up to 6 months or longer) are well described in around ten percent of individuals. The aim of this work was to characterise immunological and virological parameters in the peripheral blood, which correlate with persistence of symptoms following EBV-induced mononucleosis. Subjects were recruited prospectively following confirmed primary EBV infection, to allow blood samples and clinical data to be collected at multiple timepoints (baseline, 2 weeks, 4 weeks, 3 months and at least 12 months later). Subjects with 6 months or more of disabling symptoms were defined as ???cases??? with control subjects being those whose illness resolved within 6 weeks of enrolment. Cases were compared with control subjects in terms of: cellular EBV viral load in the peripheral blood by PCR; development of antibodies against EBV VCA (IgG and IgM) and EBNA-1 (IgG) by ELISA; proportions of peripheral blood leucocyte subsets and their activation status by flow cytometry; the magnitude, kinetics of development, and breadth of the CD8+ cytotoxic cell response by interferon-?? Elispot; cytokine levels in serum, and production by peripheral blood mononuclear cells ex vivo; and gene expression patterns in peripheral blood mononuclear cells by microarray. With the exception of gene expression, none of these parameters correlated with early resolution of symptoms or predicted clinical outcome following primary EBV infection. Antibody patterns suggest a tendency to Th2 type immune response may be associated with persistent illness. Preliminary analysis of the gene expression studies indicates that there are many genes involved in this complex disease requiring further investigation. Persistent illness following EBV infection is not associated with uncontrolled viral replication, or chronic immune activation due to an aberrant primary immune response.

Thesis (Ph.D.) -- McMaster University, 1998. / Includes bibliographical references (leaves 333-365). Also available via World Wide Web.

Thesis (M. Phil.)--University of Hong Kong, 2008. / Includes bibliographical references (leaf 102-115) Also available in print.

Thesis (Ph. D.)--Cornell University, 1989. / Vita. Includes bibliographical references.

Thesis (Ph. D.)--Ohio State University, 2004. / Document formatted into pages; contains 237 p. Includes bibliographical references. Abstract available online via OhioLINK's ETD Center; full text release delayed at author's request until 2005 Aug. 13.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1954. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 92-97).