CD40 ligation downregulates EBNA-2 and LMP-1 expression in EBV-transformed lymphoblastoid cell lines

Katja Pokrovskaja, Barbro Ehlin-Henriksson, Csaba Kiss, Anita Challa, John Gordon, Peter Gogolak, George Klein, Laszlo Szekely

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Epstein-Barr virus (EBV) drives the proliferation of human B cells in vitro and during primary infection in vivo. The transformed immunoblasts express nuclear proteins EBNA1-6, transcribed from the Cp/Wp promoter, and the membrane proteins LMP-1, -2A and -2B (lymphoblastoid type of latency). EBV persists through life in resting memory B cells with a restricted type of latency in the absence of the Cp/Wp promoter activity. Since CD40 crosslinking can reportedly inhibit the growth of EBV-transformed lymphoblastoid cell lines (LCLs), we have examined the effect of CD40 ligation on the expression of EBNAs and LMP-1 and on Cp EBV promoter activity together with several phenotypic markers. CD40 crosslinking led to a partial downregulation of EBNA-2, EBNA3-6 and LMP-1 in LCLs, paralleled by downregulation of Cp promoter activity. It also induced up-regulation of the germinal center marker CD77 on the LCL cells. Our findings suggest that the encounter of proliferating EBV-transformed immunoblasts with CD40L, as would occur when normal B cells generate memory cells in germinal centers, may switch the viral transcription program from the full lymphoblastoid to a more restricted latency program in a proportion of cells. This would permit virus persistence in the B-cell memory compartment.

Original languageEnglish
Pages (from-to)705-712
Number of pages8
JournalInternational Journal of Cancer
Volume99
Issue number5
DOIs
Publication statusPublished - Jun 1 2002

Keywords

  • CD40
  • EBNA
  • EBV
  • LMP
  • Latency

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Pokrovskaja, K., Ehlin-Henriksson, B., Kiss, C., Challa, A., Gordon, J., Gogolak, P., Klein, G., & Szekely, L. (2002). CD40 ligation downregulates EBNA-2 and LMP-1 expression in EBV-transformed lymphoblastoid cell lines. International Journal of Cancer, 99(5), 705-712. https://doi.org/10.1002/ijc.10417