Epstein-Barr and hepatitis B virus: hidden architects of viral-associated cancers

    Research output: ThesisThesis fully internal (DIV)

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    Abstract

    This double-degree PhD research investigates two important human viruses, Epstein-Barr virus (EBV) and Hepatitis B virus (HBV), both of which establish lifelong persistent infections and are associated with cancer development. Using an interdisciplinary approach that integrates molecular profiling, functional assays, bioinformatics, and epidemiology, the research aims to understand how these viruses persist, evade immune surveillance, and contribute to chronic disease and cancer, providing insight into mechanisms of viral persistence and pathogenesis.

    It examines EBV-encoded miRNAs in B cells and their role in EBV-driven B-cell lymphomas. These miRNAs regulate viral replication, latency programs, and infected B-cell survival by targeting viral and host transcripts. The miRNA profile of the largest EBV-positive classical Hodgkin lymphoma cohort was characterized and compared with EBV-positive Burkitt lymphoma, PTLD, and primary EBV infection controls. BHRF1 miRNAs were specific to PTLD, while BART miRNAs showed stable expression across groups. Highly expressed BART miRNAs were functionally validated, showing reduced cell growth or proliferation upon inhibition. GO analysis linked these miRNAs to apoptosis, proliferation, and cell cycle regulation.
    The thesis also reviews occult HBV infection (OBI) in Latin America, highlighting limited and uneven prevalence data and underestimation due to reliance on serology. A study in northeast Colombia identified OBI in 1.1% of blood donors, underscoring limitations of serological screening and the need for DNA-based testing.

    Overall, the dissertation highlights host–virus interactions driving EBV and HBV persistence and cancer risk, and supports improved diagnostic and preventive strategies.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • Diepstra, Arjan, Supervisor
    • den Berg, J.H.M.van, Supervisor, External person
    • Goyeneche, D.P., Supervisor, External person
    • Kluiver, Joost, Supervisor
    Award date5-Jan-2026
    Place of Publication[Groningen]
    Publisher
    Print ISBNs978-94-93483-62-0
    DOIs
    Publication statusPublished - 2025

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