Rapid identification and characterization of infected cells in blood during chronic active Epstein-Barr virus infection

Fournier, Benjamin; Boutboul, David; Bruneau, Julie; Miot, Charline; Boulanger, C.; Malphettes, Marion; Pellier, Isabelle; Dunogué, Bertrand; Terrier, Benjamin; Suarez, Félipe; Blanche, Stéphane; Castelle, Martin; Winter, Sarah; Delecluse, Henri Jacques; Molina, Thierry Jo; Pïcard, Capucine; Ehl, Stephan; Moshous, Despina; Galicier, Lionel; Barlogis, Vincent; Fischer, Alain; Neven, Bénédicte; Latour, Sylvain

doi:10.1084/jem.20192262

Cited by 45 publications

(50 citation statements)

References 58 publications

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“…Recently, a new flow cytometry technique combining surface marker staining with in situ hybridization for the EBER RNAs has been developed. 41,42 Sequential examination of PB using this method, without dissecting mice, shall enable us to analyze the effects of bortezomib on EBV-infected cells in vivo in more detail.…”

Section: Discussionmentioning

confidence: 99%

Antineoplastic and anti-inflammatory effects of bortezomib on systemic chronic active EBV infection

Yoshimori¹,

Shibayama

Imadome

et al. 2021

Blood Advances

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Systemic chronic active Epstein-Barr virus (EBV; sCAEBV) infection, T- and natural killer (NK)-cell type (sCAEBV), is a fatal disorder accompanied by persisting inflammation harboring clonal proliferation of EBV-infected T or NK cells. Today’s chemotherapy is insufficient to resolve disease activity and to rid infected cells of sCAEBV. The currently established treatment strategy for eradicating infected cells is allogeneic hematopoietic stem cell transplantation. In this study, we focused on the effects of proteasome inhibitor bortezomib on the disease. Bortezomib suppressed survival and induced apoptosis of EBV+ T- or NK-cell lines and peripheral mononuclear cells containing EBV-infected T or NK cells of sCAEBV patients. Bortezomib enhanced binding immunoglobulin protein/78-kDa glucose-regulated protein (Bip/GRP78) expression induced by endoplasmic reticulum stress and activated apoptosis-promoting molecules JNK and p38 in the cell lines. Bortezomib suppressed the activation of survival-promoting molecule NF-κB, which was constitutively activated in EBV+ T- or NK-cell lines. Furthermore, quantitative reverse transcription–polymerase chain reaction demonstrated that bortezomib suppressed messenger RNA expression of proinflammatory cytokines tumor necrosis factor α (TNF-α) and interferon γ (IFN-γ) in EBV+ T or NK cells from the patients. Finally, we examined the effects of bortezomib using xenograft models of sCAEBV generated by IV injection of patients’ cells. The intraperitoneal administration of bortezomib significantly reduced EBV-DNA load in peripheral blood and the infiltration of EBV-infected cells in the models’ livers. Moreover, the serum concentration of TNF-α and IFN-γ decreased after bortezomib treatment to the models. Our findings will be translated into the treatment of sCAEBV not only to reduce the number of tumor cells but also to suppress inflammation.

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Section: Discussionmentioning

confidence: 99%

Antineoplastic and anti-inflammatory effects of bortezomib on systemic chronic active EBV infection

Yoshimori¹,

Shibayama

Imadome

et al. 2021

Blood Advances

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“…Oko and coauthors concluded that this technique affords new opportunities to understand the complexity of virus infection within single cells when they observed that EBV infection (gamma herpesvirus infection in general) can be surprisingly heterogeneous at the level of the individual cell [ 82 ]. Using the PrimeFlow assay, very recently Fournier et al showed that during chronic active EBV infection, EBV-infected B cells from blood expressed PC differentiation markers [ 83 ]. Taking into consideration these achievements, the PrimeFlow assay may also be successful in EBV–periodontitis research.…”

Section: Advanced Prospective Methodsmentioning

confidence: 99%

Detection of Epstein–Barr Virus in Periodontitis: A Review of Methodological Approaches

et al. 2020

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Periodontitis, an inflammatory condition that affects the structures surrounding the tooth eventually leading to tooth loss, is one of the two biggest threats to oral health. Beyond oral health, it is associated with systemic diseases and even with cancer risk. Obviously, periodontitis represents a major global health problem with significant social and economic impact. Recently, a new paradigm was proposed in the etiopathogenesis of periodontitis involving a herpesviral–bacterial combination to promote long-term chronic inflammatory disease. Periodontitis as a risk factor for other systemic diseases can also be better explained based on viral–bacterial etiology. Significant efforts have brought numerous advances in revealing the links between periodontitis and Epstein–Barr virus (EBV), a gamma herpesvirus ubiquitous in the adult human population. The strong evidence from these studies may contribute to the advancement of periodontitis research and the ultimate control of the disease. Advancing the periodontitis research will require implementing suitable methods to establish EBV involvement in periodontitis. This review evaluates and summarizes the existing methods that allow the detection and diagnosis of EBV in periodontitis (also applicable in a more general way to other EBV-related diseases), and discusses the feasibility of the application of innovative emerging technologies.

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“…The detection of EBV-DNA in each lymphocyte fraction isolated by antibody-conjugated magnetic beads is effective to determine the phenotypes of EBV-infected cells. Recently, a new flow cytometry technique combining surface marker staining with in situ hybridization for EBER RNAs has been developed [ 20 , 21 ]. Second, I want to argue the disease definition of systemic EBV-positive T-cell lymphoma of childhood.…”

Section: The Issues On the Who 2017 Classification Which Surfacedmentioning

confidence: 99%

Chronic Active Epstein–Barr Virus Infection: The Elucidation of the Pathophysiology and the Development of Therapeutic Methods

Arai

2021

Microorganisms

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Chronic active Epstein–Barr virus infection (CAEBV) is a disease where Epstein–Barr virus (EBV)-infected T- or NK-cells are activated and proliferate clonally. The symptoms of this dual-faced disease include systemic inflammation and multiple organ failures caused by the invasion of infected cells: inflammation and neoplasm. At present, the only effective treatment strategy to eradicate EBV-infected cells is allogeneic stem cell transplantation. Lately, the investigation into the disease’s pathogenic mechanism and pathophysiology has been advancing. In this review, I will evaluate the new definition in the 2017 WHO classification, present the advancements in the study of CAEBV, and unfold the future direction.

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Rapid identification and characterization of infected cells in blood during chronic active Epstein-Barr virus infection

Cited by 45 publications

References 58 publications

Antineoplastic and anti-inflammatory effects of bortezomib on systemic chronic active EBV infection

Antineoplastic and anti-inflammatory effects of bortezomib on systemic chronic active EBV infection

Detection of Epstein–Barr Virus in Periodontitis: A Review of Methodological Approaches

Chronic Active Epstein–Barr Virus Infection: The Elucidation of the Pathophysiology and the Development of Therapeutic Methods

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