Epstein-Barr virus latent membrane protein (LMP1) is not sufficient to maintain proliferation of B cells but both it and activated CD40 can prolong their survival.

Zimber-Strobl, Ursula; Kempkes, Bettina; Marschall, Gabriele; Zeidler, Reinhard; Kooten, Cees van; Banchereau, Jacques; Bornkamm, Georg W.; Hammerschmidt, Wolfgang

doi:10.1002/j.1460-2075.1996.tb01098.x

Cited by 103 publications

(93 citation statements)

References 59 publications

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“…The proliferation induced by IL-10 in the absence of EBNA-2 in the ER/EB2-5 cells is intriguing since ectopic expression of LMP-1 in the ER/EB2-5 cells could not maintain the proliferation of these cells. 49 Furthermore IL-10 alone did not induce the proliferation of normal B cells but strongly enhanced proliferation when combined with CD40 or BCR activation. 50 Since LMP-1 mimics a constitutively active CD40 receptor, IL-10 together with LMP-1 might drive the cells into the cell cycle.…”

Section: Discussionmentioning

confidence: 93%

IL-10 can induce the expression of EBV-encoded latent membrane protein-1 (LMP-1) in the absence of EBNA-2 in B lymphocytes and in Burkitt lymphoma- and NK lymphoma-derived cell lines

Kis

Takahara

Nagy

et al. 2006

Blood

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IntroductionThe human gammaherpesvirus Epstein-Barr virus (EBV) is ubiquitous and it persists for the lifetime of the individual after the first encounter. In spite of the efficient transforming potential of the virus for B lymphocytes in vitro, the infection with EBV is largely harmless in vivo due to the vigorous immune response directed against the virus-encoded proteins expressed in proliferating cells, 1 combined with the viral strategy to downregulate the expression of the immunogenic viral proteins in the infected memory B cells. 2 A variety of lymphomas and carcinomas were found to carry EBV genome and to express virally encoded proteins. 1 Except for the lymphomas in immunosuppressed individuals, the role of the virus in the genesis of the tumors is unknown.EBV readily infects B-lymphocyte cultures in vitro and transforms them into proliferating lymphoblastoid cell lines (LCLs). These cells carry the virus in a latent form and express a set of viral genes that in concert with cellular genes induce the immunoblastic transformation and proliferation of the B cells. 1 The emerging lymphoblastoid cell lines (LCLs) express 6 nuclear (EBNA1-6) and 3 membrane viral proteins (latent membrane protein 1 [LMP-1], -2A, -2B). This expression pattern is termed type III latency or growth program. 1,2 In this program the expression of LMPs is driven by the trans-activator EBNA-2 together with EBNA-5 (EBNA-2-dependent expression of LMPs). 1 In EBV-positive malignant cells the virus expresses only a few viral genes, such as only EBNA-1 in Burkitt lymphoma (BL), whereas in nasopharyngeal carcinoma, 3 Hodgkin lymphoma, 4 and T and NK lymphomas 5 EBNA-1 is expressed together with LMP-1 and LMP-2 (EBNA-2-independent LMP expression). 1 EBER and BART RNAs are expressed in all latency forms. 1 LMP-1 is required for in vitro transformation and proliferation of B cells in vitro. 6,7 Acting as a constitutively active receptor, 8 LMP-1 activates similar pathways as the triggering of the CD40 receptor and is therefore regarded as a functional homologue of CD40.B cells with all 3 EBV latency types have been detected in the lymphoid tissues of patients with clinically manifest primary EBV infection (infectious mononucleosis [IM]) and also in healthy EBV carriers. 2 In healthy individuals, transcripts of type III latency-associated genes were found exclusively in naive B cells, whereas germinal center (GC) and memory B cells expressed the restricted type II and type I latency, respectively. 2 It has been proposed that EBV exploits the normal B-cell differentiation pathway to get access to the memory compartment. LMP-1 and LMP-2A are believed to provide survival signals for the EBV-infected GC B lymphocytes by mimicking the externally activated CD40 and B-cell receptor (BCR) pathways, respectively.Type II latent B cells were also found by immunohistochemical analysis of tonsillar sections of healthy EBV carriers 9 and IM patients. 10 Furthermore, rare B cells expressing type II EBV latency were detected in several lymphoid malignancies,...

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Section: Discussionmentioning

confidence: 93%

IL-10 can induce the expression of EBV-encoded latent membrane protein-1 (LMP-1) in the absence of EBNA-2 in B lymphocytes and in Burkitt lymphoma- and NK lymphoma-derived cell lines

Kis

Takahara

Nagy

et al. 2006

Blood

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“…In an LCL established with an EBV recombinant in which EBNA2 and LMP1 expression can be silenced, both are required for continuous proliferation and protection from apoptosis. Importantly, LMP1 expression in trans or CD40 engagement can prolong cell survival in these cells (Zimber-Strobl et al, 1996). LMP1 can also protect cells from serum starvation-, etoposide-, and p53-induced apoptosis (Fries et al, 1996;Kawanishi, 1997;Kenney et al, 1998).…”

Section: Lmp1 Protects Cells From Apoptosismentioning

confidence: 99%

Epstein-Barr virus transformation: involvement of latent membrane protein 1-mediated activation of NF-κB

1999

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“…A previous report showed that CD40 induced the production of interleukin-10 at a low dose and induced the secretion of interleukin-12 at a high dose [23]. Our previous research also showed that CD40 antibody stimulated MM cell proliferation at a low dose but induced the apoptosis of myeloma cells at a high dose [24,25]. Therefore, the infected cells may be regulated through CD40L upregulation and CD40 downregulation such that a favorable signal intensity is reached to regulate cell growth.…”

Section: Figurementioning

confidence: 72%

Effects of Epstein-Barr virus infection on the development of multiple myeloma after liver transplantation

Ye-wei

Zhao

et al. 2012

Sci. China Life Sci.

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Reduced cellular immune function in patients after liver transplantation easily results in many types of viral infections, such as Epstein-Barr virus. Epstein-Barr virus is a γ-herpesvirus and is related to many malignant diseases, especially epithelial and lymph tumors. The abnormal interaction of cluster of differentiation 40 with cluster of differentiation 40 ligand and expression of cluster of differentiation 40 ligand are considered closely related to the development of myeloma cells. This study explored the influence and mechanism of Epstein-Barr virus infection on the phenotype and biological behavior of myeloma cells after liver transplantation. Flow cytometry was used to detect coexpression of cluster of differentiation 40 and cluster of differentiation 40 ligand in 10 samples of freshly isolated multiple myeloma cells. Cluster of differentiation 40 and cluster of differentiation 40 ligand were coexpressed in sample Nos. 5, 8, 9, and 10, particularly in sample No. 5. Western blot analysis was used to detect the expression of the Epstein-Barr virus antigens latent membrane protein 1 and Epstein-Barr virus nuclear antigen 2 in the multiple myeloma cell line RPMI 8226 infected with Epstein-Barr virus. The antigen expression indicated that Epstein-Barr virus can infect multiple myeloma virus cells in vitro. Reverse transcription-polymerase chain reaction revealed upregulated expression of cluster of differentiation 40 ligand on the infected RPMI 8226 cells, which may be involved in the anti-apoptosis activity of the infected cells. Confocal microscopy showed that pairs of molecules of cluster of differentiation 40, cluster of differentiation 40 ligand, and latent membrane protein 1 were colocalized on the surface of the infected cells. CXC chemokine receptor 4 was upregulated on the RPMI 8226 cells after Epstein-Barr virus infection. The migratory ability of the infected cells improved in the presence of the chemokine stromal cell-derived factor-1α. Anti-apoptosis and migration are known important biological characteristics of malignant cells. Our results indicate the involvement of Epstein-Barr virus in the origin and development of multiple myeloma. The risk of multiple myeloma increases when Epstein-Barr virus infects B cells in the germinal center, which may result in an anti-apoptosis effect of B cells and an improved ability to migrate from the germinal center to peripheral blood.

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Epstein-Barr virus latent membrane protein (LMP1) is not sufficient to maintain proliferation of B cells but both it and activated CD40 can prolong their survival.

Cited by 103 publications

References 59 publications

IL-10 can induce the expression of EBV-encoded latent membrane protein-1 (LMP-1) in the absence of EBNA-2 in B lymphocytes and in Burkitt lymphoma- and NK lymphoma-derived cell lines

IL-10 can induce the expression of EBV-encoded latent membrane protein-1 (LMP-1) in the absence of EBNA-2 in B lymphocytes and in Burkitt lymphoma- and NK lymphoma-derived cell lines

Epstein-Barr virus transformation: involvement of latent membrane protein 1-mediated activation of NF-κB

Effects of Epstein-Barr virus infection on the development of multiple myeloma after liver transplantation

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