Abstract
Persistent infection by EBV is explained by the germinal center model (GCM) which provides a satisfying and currently the only explanation for EBVs disparate biology. Since the GCM touches on every aspect of the virus, this chapter will serve as an introduction to the subsequent chapters. EBV is B lymphotropic, and its biology closely follows that of normal mature B lymphocytes. The virus persists quiescently in resting memory B cells for the lifetime of the host in a non-pathogenic state that is also invisible to the immune response. To access this compartment, the virus infects naïve B cells in the lymphoepithelium of the tonsils and activates these cells using the growth transcription program. These cells migrate to the GC where they switch to a more limited transcription program, the default program, which helps rescue them into the memory compartment where the virus persists. For egress, the infected memory cells return to the lymphoepithelium where they occasionally differentiate into plasma cells activating viral replication. The released virus can either infect more naïve B cells or be amplified in the epithelium for shedding. This cycle of infection and the quiescent state in memory B cells allow for lifetime persistence at a very low level that is remarkably stable over time. Mathematically, this is a stable fixed point where the mechanisms regulating persistence drive the state back to equilibrium when perturbed. This is the GCM of EBV persistence. Other possible sites and mechanisms of persistence will also be discussed.
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Abbreviations
- AID:
-
Activation-induced cytidine deaminase
- AIM:
-
Acute infectious mononucleosis
- APOBEC:
-
Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like
- BAFF:
-
B cell activating factor
- BCR:
-
B cell receptor
- BL:
-
Burkitt’s lymphoma
- BLC:
-
B lymphocyte chemoattractant CXCL13
- CD40L:
-
CD40 ligand
- cIg:
-
Cytoplasmically expressed immunoglobulin
- CPM:
-
Cyclic pathogen model
- CtBP:
-
C-terminal-binding protein
- CTL:
-
Cytotoxic T cell
- DZ:
-
Dark zone
- eBL:
-
Endemic Burkitt’s lymphoma
- EBV:
-
Epstein-Barr virus
- EBNA:
-
Epstein-Barr virus nuclear antigen
- GC:
-
Germinal center
- GCM:
-
Germinal center model
- HD:
-
Hodgkin’s disease
- HEV:
-
High endothelial venules
- HIV:
-
Human immunodeficiency virus
- IE:
-
Immediate early
- Ig:
-
Immunoglobulin
- IL:
-
Immunoblastic lymphoma
- LMP:
-
Latent membrane protein
- LZ:
-
Light zone
- RBPJk:
-
Recombining binding protein
- RTPCR:
-
Real-time polymerase chain reaction
- SDF1:
-
Stromal cell-derived factor 1 CXCL12
- sIg:
-
Surface-expressed immunoglobulin
- sBL:
-
Sporadic Burkitt’s lymphoma
- Th:
-
CD4+ T helper cell
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Acknowledgments
The work described here is in large part the consequence of research carried out by a number of graduate students in my own laboratory too numerous to mention individually but hopefully appropriately referenced in the text. I would also like to express my thanks to Michael Lawson for a very careful and thorough editing of the text. To the extent that this chapter is comprehendible, it is due to him. Finally, I would like to acknowledge NIH, who have supported my laboratory continuously through Public Health Service grants R01 CA65883 and R01 AI18757.
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Thorley-Lawson, D.A. (2015). EBV Persistence—Introducing the Virus. In: Münz, C. (eds) Epstein Barr Virus Volume 1. Current Topics in Microbiology and Immunology, vol 390. Springer, Cham. https://doi.org/10.1007/978-3-319-22822-8_8
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