Jessica Reusch, PhD

Research Title: Regulation of the Latent-to-Lytic Switch of Epstein-Barr Virus by the Cellular Differentiation Factor BLIMP1

Research Summary: Cellular transcription factors involved in mediating differentiation in epithelial and B cells likely contribute to EBV reactivation out of latency into lytic replication. Trainee Jessica Reusch has been investigating the ability of the master regulator of plasma cell differentiation, BLIMP1, to induce EBV lytic reactivation (Reusch et al., manuscript in preparation). She has found that BLIMP1 expression is sufficient to induce viral reactivation in latently infected nasopharyngeal carcinoma CNE-2 cells, gastric carcinoma AGSAkata cells, undifferentiated normal oral keratinocyte (NOK)-Akata cells, and the Burkitt lymphoma (BL) cell lines Sal I and Kem III, but not the BL cell lines Mutu I and Kem I. To begin to determine the mechanism underlying this reactivation by BLIMP1, she has examined using reporter assays the effect of BLIMP1 on expression of the EBV immediate-early (IE) gene promoters, Rp and Zp; both were highly activated by this cellular transcription factor. Using deletion analysis, Jessica has localized the regions of these promoters through which this activation is mediated. Activation of Rp by BLIMP1 mapped to a 6-bp element located at -665 through -660 upstream of the Rp transcription initiation site. Activation of Zp by BLIMP1 mapped to within 83 base pairs upstream of the Zp transcription initiation site. Data from ChIP analyses indicated that BLIMP1 associates with both Rp and Zp in the context of EBV-infected cells despite not directly binding to these promoter regions in vitro in EMSAs. Thus, BLIMP1 likely associates with these key latent-lytic switch promoters as a component of transcription complexes. Taking these data together, Jessica concludes that BLIMP1 plays a direct, important role in inducing EBV lytic replication during cellular differentiation in a cell-type-dependent manner by activating expression of both of EBV’s IE genes.

Dr. Reusch is continuing her training as postdoctoral trainee at the Moffitt Cancer Center.