TY  - JOUR
AU  - Delecluse, Susanne
AU  - Baccianti, Francesco
AU  - Zala, Manon
AU  - Steffens, Alina
AU  - Drenda, Carolin
AU  - Judt, Daniel
AU  - Holland-Letz, Tim
AU  - Poirey, Remy
AU  - Sujobert, Pierre
AU  - Delecluse, Henri-Jacques
TI  - Epstein-Barr virus induces aberrant B cell migration and diapedesis via FAK-dependent chemotaxis pathways.
JO  - Nature Communications
VL  - 16
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Springer Nature
M1  - DKFZ-2025-01037
SP  - 4581
PY  - 2025
N1  - #EA:D400#LA:D400#
AB  - Infection with the Epstein-Barr virus (EBV) is a major risk factor for the development of cancer and autoimmune disorders. The virus enters the body in the pharynx, but EBV causes disease in distant organs, including the gut and the brain. Here we show, using in vitro culture and mouse infection models, that EBV-infected B cells display features of homing cells. Infected B cells undergo migration following paracrine CCL4 release and CCR1 induction, while CCR1 deficiency inhibits migration and, unexpectedly, proliferation of infected B cells. Furthermore, migrating EBV-infected B cells undergo CCL4-dependent diapedesis, induce ICAM-1 on endothelial cells, and disrupt the integrity of endothelial barriers. Both migration and diapedesis are regulated by FAK, with FAK inhibition blocking growth and survival of EBV-transformed B cells, as well as their spreading to spleen and brain in an animal model in vivo. Moreover, IL-10 secreted by EBV-infected B cells attracts and facilitates diapedesis of EBV-negative CD52highCD11c+ B cells, which have reported autoimmune properties. Our results thus provide mechanistic insight on EBV-induced B cell dysregulation, and also hint curbing migration as a potential target for reducing the pathogenicity of EBV-infected B cells.
KW  - Animals
KW  - B-Lymphocytes: virology
KW  - B-Lymphocytes: immunology
KW  - B-Lymphocytes: metabolism
KW  - Herpesvirus 4, Human: physiology
KW  - Herpesvirus 4, Human: immunology
KW  - Mice
KW  - Humans
KW  - Chemotaxis
KW  - Epstein-Barr Virus Infections: immunology
KW  - Epstein-Barr Virus Infections: virology
KW  - Epstein-Barr Virus Infections: pathology
KW  - Epstein-Barr Virus Infections: metabolism
KW  - Interleukin-10: metabolism
KW  - Cell Movement
KW  - Mice, Inbred C57BL
KW  - Receptors, CCR1: metabolism
KW  - Receptors, CCR1: genetics
KW  - Intercellular Adhesion Molecule-1: metabolism
KW  - Focal Adhesion Kinase 1: metabolism
KW  - Endothelial Cells: metabolism
KW  - Mice, Knockout
KW  - Interleukin-10 (NLM Chemicals)
KW  - Receptors, CCR1 (NLM Chemicals)
KW  - Intercellular Adhesion Molecule-1 (NLM Chemicals)
KW  - Focal Adhesion Kinase 1 (NLM Chemicals)
KW  - Ptk2 protein, mouse (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40389409
DO  - DOI:10.1038/s41467-025-59813-z
UR  - https://inrepo02.dkfz.de/record/301495
ER  -