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The Epstein-Barr virus induces the expression of the LPAM-1 integrin in B-cells in vitro and in vivo


Delecluse, Susanne; Tsai, Ming-Han; Shumilov, Anatoliy; Bencun, Maja; Arrow, Sebastian; Beshirova, Aisha; Cottignies-Calamarte, Andréa; Lasitschka, Felix; Bulut, Olcay Cem; Münz, Christian; Zeier, Martin; Behrends, Uta; Delecluse, Henri-Jacques (2019). The Epstein-Barr virus induces the expression of the LPAM-1 integrin in B-cells in vitro and in vivo. Journal of Virology, 93(5):e01618-18.

Abstract

The Epstein-Barr virus (EBV) infects the oropharynx but surprisingly frequently induces B-cell proliferations in the gut of immunosuppressed individuals. We found that EBV infection induces the expression of the LPAM-1 integrin on tonsillar B cells and increases it on peripheral blood cells. Similarly, LPAM-1 was induced in the tonsils of patients undergoing primary infectious mononucleosis. EBV-induced LPAM-1 bound to the MAdCAM-1 addressin that allows B-cell homing to the gastrointestinal mucosa-associated lymphoid tissue (GALT). Thus, we hypothesized that EBV-induced LPAM-1 could induce relocation of infected B-cells from the tonsil to the GALT. hybridization with an EBER-specific probe revealed the frequent presence of EBV-infected cells in the pericolic lymph nodes of healthy individuals. Relocation of infected B-cells into the GALT would expand the EBV reservoir, possibly protects it from T-cells primed in the oropharynx and explain why EBV induces lymphoid tumors in the gut. The Epstein-Barr virus (EBV) causes tumors in multiple organs, in particular the oro- and nasopharyngeal area, but also in the digestive system. This virus enters the body in the oropharynx and establishes a chronic infection in this area. The observation that the virus causes tumors in the digestive system implies that the infected cells can move to this organ. We found that EBV infection induces the expression of integrin beta 7 (ITGB7), an integrin that associates with integrin alpha 4 to form the LPAM-1 dimer. LPAM-1 is key for homing of B cells to the gastrointestinal tract, suggesting that induction of this molecule is the mechanism through which EBV-infected cells to enter this organ. In favor of this hypothesis, we could also detect EBV-infected cells in the lymph nodes adjacent to the colon and in the appendix.

Abstract

The Epstein-Barr virus (EBV) infects the oropharynx but surprisingly frequently induces B-cell proliferations in the gut of immunosuppressed individuals. We found that EBV infection induces the expression of the LPAM-1 integrin on tonsillar B cells and increases it on peripheral blood cells. Similarly, LPAM-1 was induced in the tonsils of patients undergoing primary infectious mononucleosis. EBV-induced LPAM-1 bound to the MAdCAM-1 addressin that allows B-cell homing to the gastrointestinal mucosa-associated lymphoid tissue (GALT). Thus, we hypothesized that EBV-induced LPAM-1 could induce relocation of infected B-cells from the tonsil to the GALT. hybridization with an EBER-specific probe revealed the frequent presence of EBV-infected cells in the pericolic lymph nodes of healthy individuals. Relocation of infected B-cells into the GALT would expand the EBV reservoir, possibly protects it from T-cells primed in the oropharynx and explain why EBV induces lymphoid tumors in the gut. The Epstein-Barr virus (EBV) causes tumors in multiple organs, in particular the oro- and nasopharyngeal area, but also in the digestive system. This virus enters the body in the oropharynx and establishes a chronic infection in this area. The observation that the virus causes tumors in the digestive system implies that the infected cells can move to this organ. We found that EBV infection induces the expression of integrin beta 7 (ITGB7), an integrin that associates with integrin alpha 4 to form the LPAM-1 dimer. LPAM-1 is key for homing of B cells to the gastrointestinal tract, suggesting that induction of this molecule is the mechanism through which EBV-infected cells to enter this organ. In favor of this hypothesis, we could also detect EBV-infected cells in the lymph nodes adjacent to the colon and in the appendix.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Experimental Immunology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Life Sciences > Microbiology
Life Sciences > Immunology
Life Sciences > Insect Science
Life Sciences > Virology
Language:English
Date:2019
Deposited On:26 Feb 2019 16:50
Last Modified:29 Jul 2020 09:44
Publisher:American Society for Microbiology
ISSN:0022-538X
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1128/JVI.01618-18
PubMed ID:30541846

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