Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.744933
Title: The virome in primary and secondary immunodeficiency
Author: Stubbs, Samuel Christopher
ISNI:       0000 0004 7230 8178
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2018
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Abstract:
The afflictions suffered by immunocompromised individuals have historically been attributed to overt infections caused by bacterial and fungal pathogens. For this reason, treatment methods have focused on resolving these infections, with great success in terms of reducing short-term morbidity and mortality rates. This initial success only served to reinforce the dogmatic opinion that to ‘cure’ immunodeficiency, one needs only to resolve and prevent recurrence of bacterial and fungal infections. However, reports of long-term health problems in immunocompromised cohorts suggest that treatment of bacterial and fungal infections alone does not resolve all aspects of the disease, and that viruses may play a greater role than previously expected. This thesis investigates whether viral infections do indeed have a significant impact in the immunocompromised patient. The overall prevalence of blood-borne viral infections in immunocompromised cohorts was determined through the combined use of unbiased, metagenomic sequencing and qPCR. The viral species detected were compared with patient records in order to determine whether there were any correlations between viral presence and patient outcome following treatment. Furthermore, by investigating a cross-section of cohorts with both inherited and acquired immunodeficiences, commonalities and differences could be found in terms of the types of viruses that infect these cohorts and their abundance in patients with different types of immunodeficiency. The findings of this work suggest that a large number of clinically undiagnosed viruses infect immunocompromised patients, however the prevalence of these viruses varies according to the form of immunodeficiency and, to a lesser extent, according to differences between individuals in the same cohort. Importantly, some of the more common viruses detected appear to be correlated with poor patient outcomes such as graft rejection and future infectious complications. Overall, these results suggest that viral infections do indeed play a larger role in the health of immunocompromised patients than has previously been thought although whether this is due to a direct cause or as a consequence is yet to be determined.
Supervisor: Heeney, Jonathan Luke Sponsor: Medical Research Council ; GlaxoSmithKline
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.744933  DOI:
Keywords: Immunodeficiency ; Virome ; Next Generation Sequencing ; Anellovirus ; Transplantation ; CVID ; Immunosuppression
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