Mouse model for acute Epstein--Barr virus infection.

Bibliographic Details
Title:	Mouse model for acute Epstein--Barr virus infection.
Authors:	Wirtz, Tristan, Weber, Timm, Sommermann, Thomas, Rajewsky, Klaus, Tomoharu Yasuda, Kracker, Sven
Source:	Proceedings of the National Academy of Sciences of the United States of America; 11/29/2016, Vol. 113 Issue 48, p13821-13826, 6p
Subject Terms:	EPSTEIN-Barr virus diseases, CELL proliferation, B cells, T cell receptors, LYMPHOPROLIFERATIVE disorders, IMMUNITY
Abstract:	Epstein--Barr Virus (EBV) infects human B cells and drives them into continuous proliferation. Two key viral factors in this process are the latent membrane proteins LMP1 and LMP2A,which mimic constitutively activated CD40 receptor and B-cell receptor signaling, respectively. EBVinfected B cells elicit a powerful T-cell response that clears the infected B cells and leads to life-long immunity. Insufficient immune surveillance of EBV-infected B cells causes life-threatening lymphoproliferative disorders, including mostly germinal center (GC)-derived B-cell lymphomas. We have modeled acute EBV infection of naive and GC B cells in mice through timed expression of LMP1 and LMP2A. Although lethal when induced in all B cells, induction of LMP1 and LMP2A in just a small fraction of naive B cells initiated a phase of rapid B-cell expansion followed by a proliferative T-cell response, clearing the LMP-expressing B cells. Interfering with T-cell activity prevented clearance of LMPexpressing B cells. This was also true for perforin deficiency, which in the human causes a life-threatening EBV-related immunoproliferative syndrome. LMP expression in GC B cells impeded the GC reaction but, upon loss of T-cell surveillance, led to fatal B-cell expansion. Thus, timed expression of LMP1 together with LMP2A in subsets of mouse B cells allows one to study major clinically relevant features of human EBV infection in vivo, opening the way to new therapeutic approaches. [ABSTRACT FROM AUTHOR]
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Database:	Complementary Index

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Items	– Name: Title Label: Title Group: Ti Data: Mouse model for acute Epstein--Barr virus infection. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Wirtz%2C+Tristan%22">Wirtz, Tristan</searchLink><br /><searchLink fieldCode="AR" term="%22Weber%2C+Timm%22">Weber, Timm</searchLink><br /><searchLink fieldCode="AR" term="%22Sommermann%2C+Thomas%22">Sommermann, Thomas</searchLink><br /><searchLink fieldCode="AR" term="%22Rajewsky%2C+Klaus%22">Rajewsky, Klaus</searchLink><br /><searchLink fieldCode="AR" term="%22Tomoharu+Yasuda%22">Tomoharu Yasuda</searchLink><br /><searchLink fieldCode="AR" term="%22Kracker%2C+Sven%22">Kracker, Sven</searchLink> – Name: TitleSource Label: Source Group: Src Data: Proceedings of the National Academy of Sciences of the United States of America; 11/29/2016, Vol. 113 Issue 48, p13821-13826, 6p – Name: Subject Label: Subject Terms Group: Su Data: <searchLink fieldCode="DE" term="%22EPSTEIN-Barr+virus+diseases%22">EPSTEIN-Barr virus diseases</searchLink><br /><searchLink fieldCode="DE" term="%22CELL+proliferation%22">CELL proliferation</searchLink><br /><searchLink fieldCode="DE" term="%22B+cells%22">B cells</searchLink><br /><searchLink fieldCode="DE" term="%22T+cell+receptors%22">T cell receptors</searchLink><br /><searchLink fieldCode="DE" term="%22LYMPHOPROLIFERATIVE+disorders%22">LYMPHOPROLIFERATIVE disorders</searchLink><br /><searchLink fieldCode="DE" term="%22IMMUNITY%22">IMMUNITY</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Epstein--Barr Virus (EBV) infects human B cells and drives them into continuous proliferation. Two key viral factors in this process are the latent membrane proteins LMP1 and LMP2A,which mimic constitutively activated CD40 receptor and B-cell receptor signaling, respectively. EBVinfected B cells elicit a powerful T-cell response that clears the infected B cells and leads to life-long immunity. Insufficient immune surveillance of EBV-infected B cells causes life-threatening lymphoproliferative disorders, including mostly germinal center (GC)-derived B-cell lymphomas. We have modeled acute EBV infection of naive and GC B cells in mice through timed expression of LMP1 and LMP2A. Although lethal when induced in all B cells, induction of LMP1 and LMP2A in just a small fraction of naive B cells initiated a phase of rapid B-cell expansion followed by a proliferative T-cell response, clearing the LMP-expressing B cells. Interfering with T-cell activity prevented clearance of LMPexpressing B cells. This was also true for perforin deficiency, which in the human causes a life-threatening EBV-related immunoproliferative syndrome. LMP expression in GC B cells impeded the GC reaction but, upon loss of T-cell surveillance, led to fatal B-cell expansion. Thus, timed expression of LMP1 together with LMP2A in subsets of mouse B cells allows one to study major clinically relevant features of human EBV infection in vivo, opening the way to new therapeutic approaches. [ABSTRACT FROM AUTHOR] – Name: Abstract Label: Group: Ab Data: <i>Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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RecordInfo	BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1073/pnas.1616574113 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 6 StartPage: 13821 Subjects: – SubjectFull: EPSTEIN-Barr virus diseases Type: general – SubjectFull: CELL proliferation Type: general – SubjectFull: B cells Type: general – SubjectFull: T cell receptors Type: general – SubjectFull: LYMPHOPROLIFERATIVE disorders Type: general – SubjectFull: IMMUNITY Type: general Titles: – TitleFull: Mouse model for acute Epstein--Barr virus infection. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Wirtz, Tristan – PersonEntity: Name: NameFull: Weber, Timm – PersonEntity: Name: NameFull: Sommermann, Thomas – PersonEntity: Name: NameFull: Rajewsky, Klaus – PersonEntity: Name: NameFull: Tomoharu Yasuda – PersonEntity: Name: NameFull: Kracker, Sven IsPartOfRelationships: – BibEntity: Dates: – D: 29 M: 11 Text: 11/29/2016 Type: published Y: 2016 Identifiers: – Type: issn-print Value: 00278424 Numbering: – Type: volume Value: 113 – Type: issue Value: 48 Titles: – TitleFull: Proceedings of the National Academy of Sciences of the United States of America Type: main
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