Description:

Title: Epigenetic Control of the Epstein-Barr Virus B cell Lytic Switch

Speaker:  Benjamin Gewurz, MD, PhD, Associate Professor, Division of Infectious Diseases, Brigham & Women’s Hospital, Harvard Medical School, Broad Institute

Topic:

Epstein-Barr virus infects 95% of adults worldwide, is associated with 200,000 cancers/year including Burkitt, Hodgkin and post-transplant lymphomas. EBV uses a biphasic lifecycle, in which it alternates between latency and lytic reactivation states to successfully colonize the B-cell compartment and to spread between hosts. EBV uses latency to evade immune detection  in reservoir memory B-cells and in most tumors. Consequently, there is growing interest in lytic reactivation therapy, in which reactivation of EBV lytic gene expression sensitizes EBV-infected cancer cells to the antiviral ganciclovir and to antiviral immune responses.  However, much remains to be learned about the epigenetic mechanisms that trigger the double stranded DNA viral genome to reactivate, in which expression of nearly 80 viral genes is rapidly de-repressed.  We used human genome-wide CRISPR/Cas9 screens to identify key epigenetic mechanisms at the heart of the EBV lytic switch, revealing key roles for viral non-coding RNAs and higher order EBV genome architecture.

Host: Eva Gottwein, PhD, Associate Professor, Dept. of Microbiology-Immunology