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CD40 ligation downregulates EBNA‐2 and LMP‐1 expression in EBV‐transformed lymphoblastoid cell lines
Author(s) -
Pokrovskaja Katja,
EhlinHenriksson Barbro,
Kiss Csaba,
Challa Anita,
Gordon John,
Gogolak Peter,
Klein George,
Szekely Laszlo
Publication year - 2002
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.10417
Subject(s) - ligation , lymphoblast , cell culture , virology , cancer research , biology , immunology , microbiology and biotechnology , genetics
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 upregulation 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. © 2002 Wiley‐Liss, Inc.