We are interested in defining the underlying heterogeneity of individual EBV-infected cells to learn how cell fate decisions are made such as proliferation versus arrest or death, latency versus lytic/productive infection, and how the virus/host interactions controlling these decisions are regulated in individual cells. Recently, we performed single cell RNA sequencing on EBV-immortalized LCLs and made the surprising observation that the well-described activation of the NFkB pathway in LCLs was opposed by a B-cell differentiation program. While the broad distribution of NFkB activation within LCLs was known, the dichotomy of an opposing differentiated population was not. In recent work, we have begun to characterize this plasticity using genetic reporters of the underlying molecular circuitry. Our work is partly guided by the mouse B cell maturation model of activation and differentiation into antibody-secreting cells as well as what is known of how EBV co-opts these transcriptional pathways. Finally, we posit that EBV latently infected cells promote B-cell differentiation to access transcription factors that promote lytic reactivation of the virus. While this phenotype is selected against in cell culture, it is likely an important trigger for virus production in vivo. This work is currently supported by an R01 from NIDCR. Check out one of our papers here!
Elliott Nico Gillian
Lauren Ali David