Functional Epstein-Barr virus reservoir in plasma cells derived from infected peripheral blood memory B cells.
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.
Department of Virology, University Medical Center, Montpellier, France.
Yassine
Y
Al Tabaa
Edouard
E
Tuaillon
Karine
K
Bollore
Vincent
V
Foulongne
Gael
G
Petitjean
Jean-Marie
JM
Seigneurin
Christophe
C
Duperray
Claude
C
Desgranges
Jean-Pierre
JP
Vendrell
D000328:Adult; D001402:B-Lymphocytes / Q000378:metabolism / Q000821:virology*; D002478:Cells, Cultured; D004279:DNA, Viral / Q000032:analysis; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000276:immunology / Q000821:virology*; D005434:Flow Cytometry; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D010950:Plasma Cells / Q000378:metabolism / Q000821:virology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism; D014775:Virus Activation / Q000502:physiology*; D017735:Virus Latency / Q000502:physiology
C063676:BZLF1 protein, Herpesvirus 4, Human; D004279:DNA, Viral; D015534:Trans-Activators; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7