Epstein-Barr and hepatitis B virus: hidden architects of viral-associated cancers
Epstein-Barr and hepatitis B virus: hidden architects of viral-associated cancers
This PhD research in the context of a double degree focuses on two important human viruses, the Epstein-Barr virus (EBV) and the hepatitis B virus (HBV). They can cause lifelong infections and are linked to cancer. By combining molecular profiling, assays, bioinformatics and epidemiology, this research seeks to understand the mechanisms by which these viruses persist, evade immunity and contribute to disease and cancer, and thus gain insight into the pathogenesis of viral infections.
The research will study EBV-encoded microRNAs in B cells and their role in EBV-driven B cell lymphomas. These microRNAs regulate viral replication, latency programs, and the survival of infected B cells by targeting both viral and cellular transcripts. The microRNA profile of the largest cohort of EBV-positive classical Hodgkin lymphomas was characterized and compared with EBV-positive Burkitt lymphomas, PTLD, and controls with primary EBV infection. BHRF1 microRNAs were specific to PTLD, while BART microRNAs showed stable expression in all groups. Functional validation of highly expressed BART microRNAs showed reduced cell growth or proliferation after inhibition. GO analysis linked these microRNAs to apoptosis, proliferation, and cell cycle regulation.
In addition, the dissertation discusses occult HBV infection (OBI) in Latin America, highlighting limited and unevenly distributed prevalence data and underestimation through the use of serological tests. A study in northeastern Colombia identified OBI in 1.1% of blood donors, underlining the limitations of serological screening and the need for DNA-based testing.
In summary, this dissertation highlights the host-virus interactions underlying the persistence of EBV and HBV and the associated cancer risk, and supports the development of improved diagnostic and preventive strategies.