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Blood, 15 January 2009, Vol. 113, No. 3, pp. 604-611.
Prepublished online as a Blood First Edition Paper on October 9, 2008; DOI 10.1182/blood-2008-02-136903.


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Submitted February 1, 2008
Accepted September 15, 2008

Functional Epstein-Barr virus reservoir in plasma cells derived from infected peripheral blood memory B cells

Yassine Al Tabaa, Edouard Tuaillon, Karine Bollore, Vincent Foulongne, Gael Petitjean, Jean-Marie Seigneurin, Christophe Duperray, Claude Desgranges, and Jean-Pierre Vendrell*

Department of Virology, University Medical Center of Montpellier, Montpellier, France
Department of Virology, University Medical Center of Grenoble, Grenoble, France
INSERM U847, Montpellier, France
Institut Cochin, Universite Rene Descartes, CNRS (UMR 8104), Paris, France

* Corresponding author; email: jp-vendrell{at}chu-montpellier.fr.

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 9/13 subjects, EBV-DNA quantification in B cell culture supernatants gave evidence of the 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.


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