Epigenetic crossroads of the Epstein-Barr virus B-cell relationship

Publication date: October 2018Source: Current Opinion in Virology, Volume 32Author(s): Thomas C Frost, Benjamin E GewurzEpstein-Barr virus (EBV) is a gamma-herpesvirus that establishes lifelong infection in the majority of people worldwide. EBV uses epigenetic reprogramming to switch between multiple latency states in order to colonize the memory B-cell compartment and to then periodically undergo lytic reactivation upon plasma cell differentiation. This review focuses on recent advances in the understanding of epigenetic mechanisms that EBV uses to control its lifecycle and to subvert the growth and survival pathways that underly EBV-driven B-cell differentiation versus B-cell growth transformation, a hallmark of the first human tumor virus. These include the formation of viral super enhancers that drive expression of key host dependency factors, evasion of tumor suppressor responses, prevention of plasmablast differentiation, and regulation of the B-cell lytic switch.Graphical abstractKey epigenetic mechanisms regulating EBV and B-cell gene expression. Upon B-cell infection, the EBV genome rapidly becomes chromatinized to establish latency. During latency III, EBV super-enhancers, comprised of four EBNA and five NF-kB transcription factor subunts target key host growth and survival genes, including IRF4. EBNA2 superenhancers target additional key host dependency factors, including BATF. Separately, EBNA3A, 3C and polycomb proteins block expression of tumor suppressors, incl...

Source: Current Opinion in Virology - September 16, 2018 Category: Virology Source Type: research