Challenging the dogma of latency in Epstein-Barr virus associated diseases: are there more ‘latent’ genes than we thought? (360G-Wellcome-202419_Z_16_Z)

This project aims to address a fundamental question in the biology of Epstein-Barr virus (EBV) infection; namely, how do we define which viral genes are associated with viral latency? It is well established that the EBV genome codes for around 90 genes, a subset of which (known as the latency genes) are critical for EBV-driven growth transformation of primary B cells in vitro. The remaining genes are involved in viral DNA replication, virus assembly and virus egress and are only thought to be expressed in productively infected cells. However, we and others have recently shown that the pattern of EBV transcription in apparently latently infected cells is more complex than was previously thought and extends beyond the subset of traditional latency-associated genes. Here we shall focus on three of these recently identified genes, LF1, LF2 and LF3, which are poorly characterised. Using a combination of in situ hybridisation and flow cytometry, we shall screen for LF1-3 transcripts in EBV-infected cells and virus-positive tumour lines at the single cell level and ask whether these transcripts really are expressed in the absence of other markers of lytic replication.