Epstein-Barr virus latency: current and future perspectives

Kempkes, Bettina; Robertson, Erle S.

doi:10.1016/j.coviro.2015.09.007

Cited by 93 publications

(87 citation statements)

References 49 publications

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“…Several viral nuclear proteins are involved in establishment of latency (EBNA2, EBNA3A, 3B, 3C, and leader protein or LP), which control transcription of viral and host genes via interactions with the key effector of canonical Notch signaling, RBPJκ (Raab-Traub, 2012). In established NPC, these viral proteins are not detected, and two other EBV latent genes with well demonstrated transforming properties are instead expressed (Kempkes and Robertson, 2015). One codes for LMP1 (Latent membrane protein 1), which functions as an activated TNF family member and can activate multiple pathways, including MAPK/JNK, PI3K/AKT and NF-κB.…”

Section: Etiology Of Sccsmentioning

confidence: 99%

Squamous Cell Cancers: A Unified Perspective on Biology and Genetics

2016

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SUMMARY Squamous cell carcinomas (SCCs) represent the most frequent human solid tumors and a major cause of cancer mortality. These highly heterogeneous tumors arise from closely interconnected epithelial cell populations with intrinsic self-renewal potential inversely related to the stratified differentiation program. SCCs can also originate from simple or pseudo-stratified epithelia through activation of quiescent cells and/or a switch in cell fate determination. Here, we focus on specific determinants implicated in the development of SCCs by recent large-scale genomic, genetic and epigenetic studies and complementary functional analysis. This evidence indicates that SCCs from various body sites, while clinically treated as separate entities, have common determinants, pointing to a unified perspective of the disease and potential new avenues for prevention and treatment.

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Section: Etiology Of Sccsmentioning

confidence: 99%

Squamous Cell Cancers: A Unified Perspective on Biology and Genetics

2016

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“…Epstein-Barr virus (EBV) is a member of the gamma herpesvirus family that infects B lymphocytes in more than 90% of the world population (Kang and Kieff, 2015; Kempkes and Robertson, 2015). While most infections are asymptomatic or result in infectious mononucleosis (Thorley-Lawson et al, 2013), EBV is associated with the development of multiple autoimmune diseases and lymphomas of the immune system (Ascherio and Munger, 2015; Thorley-Lawson and Gross, 2004).…”

Section: Introductionmentioning

confidence: 99%

Epstein-Barr Virus Latent Membrane Protein 2A (LMP2A) enhances IL-10 production through the activation of Bruton's tyrosine kinase and STAT3

et al. 2017

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Previous data demonstrate that Epstein-Barr Virus Latent Membrane Protein 2A (LMP2A) enhances IL-10 to promote the survival of LMP2A-expressing B cell lymphomas. Since STAT3 is an important regulator of IL-10 production, we hypothesized that LMP2A activates a signal transduction cascade that increases STAT3 phosphorylation to enhance IL-10. Using LMP2A-negative and –positive B cell lines, the data indicate that LMP2A requires the early signaling molecules of the Syk/RAS/PI3K pathway to increase IL-10. Additional studies indicate that the PI3K-regulated kinase, BTK, is responsible for phosphorylating STAT3, which ultimately mediates the LMP2A-dependent increase in IL-10. These data are the first to show that LMP2A signaling results in STAT3 phosphorylation in B cells through a PI3K/BTK-dependent pathway. With the use of BTK and STAT3 inhibitors to treat B cell lymphomas in clinical trials, these findings highlight the possibility of using new pharmaceutical approaches to treat EBV-associated lymphomas that express LMP2A.

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“…The disease is associated with Epstein-Barr virus (EBV) infection of the malignant cells and is most frequently found in areas with holoendemic malaria. Most people become infected with EBV during their lifetime without any apparent consequences (3). However, latent EBV-infected B-cells can be reactivated in settings of congenital or acquired immunosuppression leading to the establishment and polyclonal outgrowth that result in BL (4-8).…”

Section: Introductionmentioning

confidence: 99%

Burkitt lymphoma expresses oncofetal chondroitin sulfate without being a reservoir for placental malaria sequestration

Agerbæk

Pereira

Clausen

et al. 2017

Intl Journal of Cancer

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Burkitt lymphoma (BL) is a malignant disease, which is frequently found in areas with holoendemic Plasmodium falciparum malaria. We have previously found that the VAR2CSA protein is present on malaria-infected erythrocytes and facilitates a highly specific binding to the placenta. OfCS is absent from other non-malignant tissues and thus VAR2CSA generally facilitates parasite sequestration and accumulation in pregnant women. In this study, we show that the specific receptor for VAR2CSA, the oncofetal chondroitin sulfate (ofCS), is likewise present in BL tissue and cell lines. We therefore explored whether ofCS in BL could act as anchor-site for VAR2CSA-expressing infected erythrocytes. In contrast to the placenta, we found no evidence of in vivo sequestering of infected erythrocytes in the BL tissue. Furthermore, we found VAR2CSA specific antibody titers in children with endemic BL to be lower than in control children from the same malaria endemic region. The abundant presence of ofCS in BL tissue and the absence of ofCS in non-malignant tissue, encouraged us to examine whether recombinant VAR2CSA could be used to target BL. We confirmed the binding of VAR2CSA to BL-derived cells and showed that a VAR2CSA drug conjugate efficiently killed the BL-derived cell lines in vitro. These results identify ofCS as a novel therapeutic BL target and highlight how VAR2CSA could be used as a tool for the discovery of novel approaches for directing BL therapy.

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Epstein-Barr virus latency: current and future perspectives

Cited by 93 publications

References 49 publications

Squamous Cell Cancers: A Unified Perspective on Biology and Genetics

Squamous Cell Cancers: A Unified Perspective on Biology and Genetics

Epstein-Barr Virus Latent Membrane Protein 2A (LMP2A) enhances IL-10 production through the activation of Bruton's tyrosine kinase and STAT3

Burkitt lymphoma expresses oncofetal chondroitin sulfate without being a reservoir for placental malaria sequestration

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