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Investigations into the pathogenesis of human cytomegalovirus

Cope, Alethea Gwendoline Victoria; (1998) Investigations into the pathogenesis of human cytomegalovirus. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Human cytomegalovirus (HCMV), a member of the betaherpesviruses is a major cause of morbidity and mortality in the immunocompromised host. However, the pathogenesis of HCMV disease still remains unclear. This thesis has investigated the pathogenesis of HCMV in the immunocompromised host. Quantitative polymerase chain reaction (PCR) methods were used for the longitudinal measurement of HCMV viral load in congenitally infected infants and recipients of renal and liver transplants. The association between HCMV viral load and HCMV disease in the context of other risk factors for disease and response to antiviral therapy was examined. Measurement of HCMV load was found to provide important prognostic information and allowed the effects of antiviral therapy on virus clearance to be assessed. Elevated viral load was significantly associated with risk of HCMV disease in renal and liver transplant recipients (p<0.01 and p<0.0001, respectively). In addition, elevated HCMV viral load remained an independent risk factor following multivariate analysis in both transplant populations. In contrast, the risk of donor seropositivity was negated after controlling for HCMV viral load in both renal and liver transplant recipients indicating that this is the mechanism through which this risk factor operates. The administration of augmented methylprednisolone for rejection episodes in liver transplant recipients was also identified as an independent risk factor for disease in liver transplant recipients and acted to reduce the viral load level required to produce disease. The dynamics of anti-gB antibody levels in liver transplant recipients was investigated. In theses individuals, the timing and level of specific anti-gB antibodies was significantly associated with the level and timing of appearance of HCMV DNAemia. Finally I developed and optimised a fully quantitative reverse transcriptase PCR assay (QCRT-PCR) for the detection of HCMV gB mRNA with a view to providing further information into the dynamics of HCMV gB expression and in monitoring antiviral efficacy.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Investigations into the pathogenesis of human cytomegalovirus
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences; Health and environmental sciences; Cytomegalovirus
URI: https://discovery.ucl.ac.uk/id/eprint/10106566
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