Epstein-Barr virus infectious particles initiate B cell transformation and modulate cytokine response

The Epstein-Barr virus efficiently transforms primary B cells. In this thesis I show that this process starts immediately after cellular exposure to viral particles that activate STAT3 and p38/MK2, resulting in the expression of viral transforming genes. Indeed, virus binding to B cells led to activation of intracytoplasmic tyrosine kinases and of STAT3. Tegument proteins within the virion in turn activated the p38-MK2-ZFP36L1 pathway upon cellular entry, independently of the viral DNA. ZFP36L1 is a stress response protein that targets transcripts with an AU-rich 3’UTR and accordingly reduced IL-6 and TNFα transcription in infected cells. Expression of viral latent proteins after infection amplified the viral effects on p38 and MK2, but also on ZFP36L1, altogether resulting in a transitory and limited increase in IL-6 and TNFα transcription and secretion. However, cytokine release was much stronger in some individuals, which might have clinical consequences. p38 or STAT3 inactivation largely inhibited latent gene transcription without impeding infection itself, showing that proteins present in the virion influence events independent of virus entry. Thus, EBV virions are not merely vehicles that allow injection of the viral DNA into the nucleus, but manipulate cellular pathways to initiate transformation while modulating cytokine release

The EBMT Handbook

This Open Access edition of the European Society for Blood and Marrow Transplantation (EBMT) handbook addresses the latest developments and innovations in hematopoietic stem cell transplantation and cellular therapy. Consisting of 93 chapters, it has been written by 175 leading experts in the field. Discussing all types of stem cell and bone marrow transplantation, including haplo-identical stem cell and cord blood transplantation, it also covers the indications for transplantation, the management of early and late complications as well as the new and rapidly evolving field of cellular therapies. This book provides an unparalleled description of current practices to enhance readers’ knowledge and practice skills