Functional Epstein-Barr virus reservoir in plasma cells derived from infected peripheral blood memory B cells
| Autor: | Claude Desgranges, Jean-Marie Seigneurin, Jean-Pierre Vendrell, Christophe Duperray, Gaël Petitjean, Karine Bollore, Vincent Foulongne, Edouard Tuaillon, Yassine Al Tabaa |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Epstein-Barr Virus Infections Herpesvirus 4 Human Plasma Cells Immunology medicine.disease_cause Biochemistry Immunoglobulin D Virus Antigen hemic and lymphatic diseases Plasma cell differentiation medicine Humans Cells Cultured B-Lymphocytes biology Reverse Transcriptase Polymerase Chain Reaction ELISPOT Cell Biology Hematology Flow Cytometry Epstein–Barr virus Virology Tumor Necrosis Factor Receptor Superfamily Member 7 Virus Latency BZLF1 Lytic cycle DNA Viral Trans-Activators biology.protein Virus Activation Immunologic Memory |
| Zdroj: | Blood. 113:604-611 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | The Epstein-Barr virus (EBV) causes infectious mononucleosis, establishes latency in resting memory B lymphocytes, and is involved in oncogenesis through poorly understood mechanisms. The EBV lytic cycle is initiated during plasma cell differentiation by mRNAs transcripts encoded by BZLF1, which induce the synthesis of EBV proteins such as the immediate-early antigen ZEBRA and the late membrane antigen gp350. Therefore, we assessed the capacity of circulating EBV-infected B lymphocytes from healthy EBV-seropositive subjects to enter and complete the EBV lytic cycle. Purified B lymphocytes were polyclonally stimulated and BZLF1- or gp350-secreting cells (BZLF1-SCs or gp350-SCs) were enumerated by ELISpot assays. The number of BZLF1-SCs ranged from 50 to 480/107 lymphocytes (median, 80; 25th-75th percentiles, 70-150) and gp350-SCs from 10 to 40/107 lymphocytes (median, 17; 25th-75th percentiles, 10-20). gp350-SCs represented only 7.7% to 28.6% of BZLF1-SCs (median, 15%; 25th-75th percentiles, 10.5%-20%). This EBV functional reservoir was preferentially restricted to plasma cells derived from CD27+ IgD− memory B lymphocytes. In 9 of 13 subjects, EBV DNA quantification in B-cell culture supernatants gave evidence of completion of EBV lytic cycle. These results demonstrate that EBV proteins can be secreted by EBV-infected B lymphocytes from healthy carriers, a majority generating an abortive EBV lytic cycle and a minority completing the cycle. |
| Databáze: | OpenAIRE |
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