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

• Published in: The Journal of experimental medicine Vol. 217; no. 11
• Main Authors: Fournier, Benjamin, Boutboul, David, Bruneau, Julie, Miot, Charline, Boulanger, Cécile, Malphettes, Marion, Pellier, Isabelle, Dunogué, Bertrand, Terrier, Benjamin, Suarez, Felipe, Blanche, Stéphane, Castelle, Martin, Winter, Sarah, Delecluse, Henri-Jacques, Molina, Thierry, Picard, Capucine, Ehl, Stephan, Moshous, Despina, Galicier, Lionel, Barlogis, Vincent, Fischer, Alain, Neven, Bénédicte, Latour, Sylvain
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 02.11.2020
• Subjects: Adult; B-Lymphocytes - metabolism; B-Lymphocytes - virology; Child; Child, Preschool; Chronic Disease; Epstein-Barr Virus Infections - blood; Epstein-Barr Virus Infections - complications; Epstein-Barr Virus Infections - diagnosis; Epstein-Barr Virus Infections - virology; Female; Flow Cytometry - methods; Herpesvirus 4, Human - metabolism; Humans; Immunodeficiency; In Situ Hybridization, Fluorescence - methods; Infectious disease and host defense; Killer Cells, Natural - metabolism; Killer Cells, Natural - virology; Leukemia & Lymphoma; Life Sciences; Lymphoproliferative Disorders - blood; Lymphoproliferative Disorders - diagnosis; Lymphoproliferative Disorders - etiology; Male; Phenotype; RNA, Viral - analysis; RNA, Viral - metabolism; T-Lymphocytes - metabolism; T-Lymphocytes - virology; Technical Advances and Resources; Viral Load
• ISSN: 0022-1007; 1540-9538; 1540-9538
• DOI: 10.1084/jem.20192262

Epstein-Barr virus (EBV) preferentially infects epithelial cells and B lymphocytes and sometimes T and NK lymphocytes. Persistence of EBV-infected cells results in severe lymphoproliferative disorders (LPDs). Diagnosis of EBV-driven T or NK cell LPD and chronic active EBV diseases (CAEBV) is difficult, often requiring biopsies. Herein, we report a flow-FISH cytometry assay that detects cells expressing EBV-encoded small RNAs (EBERs), allowing rapid identification of EBV-infected cells among PBMCs. EBV-infected B, T, and/or NK cells were detectable in various LPD conditions. Diagnosis of CAEBV in 22 patients of Caucasian and African origins was established. All exhibited circulating EBV-infected T and/or NK cells, highlighting that CAEBV is not restricted to native American and Asian populations. Proportions of EBV-infected cells correlated with blood EBV loads. We showed that EBV-infected T cells had an effector memory activated phenotype, whereas EBV-infected B cells expressed plasma cell differentiation markers. Thus, this method achieves accurate and unambiguous diagnoses of different forms of EBV-driven LPD and represents a powerful tool to study their pathophysiological mechanisms.