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Permanent link (DOI): https://doi.org/10.7939/R3V980074

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Determinants of Cytomegalovirus Infection Outcomes in Solid Organ Transplant Recipients Open Access

Descriptions

Other title
Subject/Keyword
cytomegalovirus
transplantation
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Lisboa, Luiz
Supervisor and department
Tyrrell, D. Lorne (Medicine)
Humar, Atul (Medicine)
Kumar, Deepali (Medicine)
Examining committee member and department
Nagendran, Jayan (Surgery)
Kumar, Deepali (Medicine)
Hemmings, Denise (Obstetrics & Gynecology)
Tibbles, Lee Ann (Medicine - University of Calgary)
Pang, Xiaoli (Laboratory Medicine & Pathology)
Humar, Atul (Medicine)
McMurtry, M. Sean (Medicine)
Tyrrell, D. Lorne (Medicine)
Department
Department of Medicine
Specialization
Experimental Medicine
Date accepted
2014-12-23T15:33:25Z
Graduation date
2015-06
Degree
Doctor of Philosophy
Degree level
Doctoral
Abstract
Cytomegalovirus (CMV) is the most common opportunistic post-transplant infection. Although important advances have been made in the management and prevention of post-transplant CMV, current strategies for monitoring and prevention still show significant limitations. Such gaps create opportunities to understand the determinants of viremia and disease episodes that occur despite the use of antiviral prophylaxis and pre-emptive antiviral therapy. Straddling the boundaries between clinical and basic science, in this PhD thesis I explore the potential utility and limitations of both molecular and immunological biomarker monitoring of Cytomegalovirus in predicting viral replication/disease and assessing therapeutic response. Additionally, I investigate the biological relevance of selected viral and host biomarkers as determinants of viral infection outcomes. This thesis is comprised of a series of 5 studies in which I examine the use of: viral DNA monitoring to assess responses to antiviral therapy during CMV disease (Chapter 2); viral DNA monitoring to predict viral replication/disease post antiviral prophylaxis (Chapter 3); interferon-gamma monitoring in the virus-specific immune response during viral replication (Chapter 4); host chemokine monitoring in the virus-specific immune response during viral replication (Chapter 5); and virus microRNA monitoring to assess the response to antiviral therapy during Cytomegalovirus disease (Chapter 6). Together, these studies highlight novel aspects of the virus-host interaction that contribute to the regulation, or loss thereof, of CMV replication in solid organ transplant recipients.
Language
English
DOI
doi:10.7939/R3V980074
Rights
This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for the purpose of private, scholarly or scientific research. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
Citation for previous publication
L.F. Lisboa, A. Åsberg, D. Kumar, X.L. Pang, A. Hartmann, J.K. Preiksaitis, M.D. Pescovitz, H. Rollag, A.G. Jardine, A. Humar, “The Clinical Utility of Whole Blood versus Plasma Cytomegalovirus Viral Load Assays for Monitoring Therapeutic Response”, Transplantation, vol. 91, issue 2, 231-236L.F. Lisboa, J.K. Preiksaitis, A. Humar, D. Kumar, “Clinical Utility of Molecular Surveillance for Cytomegalovirus after Antiviral Prophylaxis in High-Risk Solid Organ Transplant Recipients“, Transplantation, vol. 92, issue 9, 1063-1068L.F. Lisboa, D. Kumar, L.E. Wilson, A. Humar, “Clinical Utility of Cytomegalovirus Cell-Mediated Immunity in Transplant Recipients with Cytomegalovirus Viremia”, Transplantation, vol. 93, issue 2, 195-200

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