Kidd, Ian Michael; (1997) Human cytomegalovirus, human herpesvirus 6 and human herpesvirus 7 infection of the immunocompromised host. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Human cytomegalovirus (HCMV) is a betaherpesvirus shown to be a major cause of disease in immunocompromised hosts. Human herpesviruses 6 and 7 (HHV-6 and HHV- 7) show genetic homology to HCMV, and are classified in the same subfamily. Their role in disease of the immunocompromised is unclear. This thesis shows that the polymerase chain reaction (PCR) can be used to provide important information about the natural history of these viruses in healthy and immunocompromised individuals. PCR assays for the detection of HCMV in blood were used in the surveillance of solid- organ and bone-marrow transplant groups, and important prognostic information was obtained about development of HCMV disease. In this case, the benefits of this earlier diagnosis allowed more effective patient management strategies to be formulated. These studies were extended to detect and analyse HHV-6 and HHV-7 infections. An HHV-7 genome library was constructed and primers designed to amplify an HHV-7 genome region of likely conservation. Following optimisation and calibration of qualitative, multiplex and quantitative-competitive PCR assays, an analysis of the natural history of these viruses in healthy individuals showed that viral load associated with persistence is lower and more stable in blood than in saliva. The role of HHV-6 and HHV-7 primary infection in febrile illness of infants was then investigated, identifying primary infections by a high blood viral load together with the absence of detectable virus in the saliva. Both HHV-6 and HHV-7 were associated with convulsions in infected infants. Finally, a detailed clinico-pathologic analysis of renal transplant patients showed a significant association between development of HCMV disease and infection with both HCMV and HHV-7, but not with HCMV alone. In addition, HHV-7 infection alone was associated with more episodes of graft rejection. These data suggest a role for HHV-7 as an important co-factor in the development of HCMV disease.

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