Epstein-Barr virus and cellular DNA damage response

Sejic, Nenad (2014). Epstein-Barr virus and cellular DNA damage response. University of Birmingham. M.Res.


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EBV is an oncogenic human gammaherpesvirus which infects B lymphocytes and epithelial cells. New virus replication occurs in both cell types and EBV encodes proteins to replicate its own DNA. Selective activation of the DNA damage response (DDR) is thought to occur in order for the virus to efficiently conserve its DNA sequence. Components of the double strand break homologous repair pathway are known to be recruited to viral replication compartments and loaded onto viral DNA to achieve efficient and faithful replication of the viral DNA.
Using an epithelial cell line latently infected with EBV, we demonstrated interactions between the phosphorylated replication protein A (RPA) and the viral lytic proteins BALF2 (DNA binding protein) and BMRF1 (polymerase accessory factor). However, despite its presence at replication centres, we failed to identify its direct interaction with the viral proteins by co-immunoprecipitation and mass spectrometry. Analysis of viral gene expression after ATM inhibition suggests that ATM does not promote the expression EBV lytic genes and is perhaps inhibitory. However, we did identify a novel interaction between BALF2 and the mitochondrial H+-Ca2+ exchanger LETM1, suggesting a new role for BALF2 possibly in inhibition of apoptosis during the viral lytic cycle.

Type of Work: Thesis (Masters by Research > M.Res.)
Award Type: Masters by Research > M.Res.
College/Faculty: Colleges (2008 onwards) > College of Medical & Dental Sciences
School or Department: Institute of Cancer Studies
Funders: None/not applicable
Subjects: R Medicine > RC Internal medicine
URI: http://etheses.bham.ac.uk/id/eprint/5506


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