Effects of n-Butyrate on Epstein--Barr Virus-carrying Lymphoma Lines

Abstract

SUMMARY n-Butyrate has been shown to induce Epstein-Barr virus (EBV) antigen synthesis in certain EBV-carrying lymphoma lines . We have studied the effect of n-butyrate on two EBV-positive Burkitt lymphoma lines by immunofluorescence and electron microscopy. In the producer line P3HR-1, the drug induced not only early antigen (EA) and virus capsid antigen (VCA) synthesis, as shown before, but also increased the number of cells containing virus particles. The transition from VCA expression to the formation of virus particles was much more effective in treated cells than in EBV antigen-producing cells of the same line. The productive cycle was associated with the development of characteristic morphological changes. In the non-producer Raji cells, n-butyrate induced EA in only a minor fraction of the cells. There were, however, clear signs of differentiation in the direction of plasma cells. Two days after the addition of n-butyrate 80 % of the Raji cells could be classified as plasmablasts. After 72 h, 20% of the cells appeared as typical plasma cells.

Effect of <i>n</i>-Butyrate on Transformation of Human Lymphocytes by Epstein-Barr Virus

“…The mode of action of «-butyrate on EBNA synthesis may be indirect, and one of the following characteristics may be involved in its effect on EBV-induced transform ation: (i) The drug can induce a virus lytic cycle in some lymphoblastoid cell lines [5], and (ii) it can induce cell differentiation [13]. As for the first possibility, no antigens of a productive virus cycle were detected in our experiments.…”

Plasma Cell-Specific Transcription Factor XBP-1s Binds to and Transactivates the Epstein-Barr Virus BZLF1 Promoter

“…These changes in chromatin structure would render the immediate-early genes of EBV accessible for the transcription machinery. Sodium butyrate, for example, has been documented to stimulate B-cell terminal differentiation and viral lytic induction in the Raji Burkitt's lymphoma cell line, giving a strong indication that chromatin changes associated with plasma cell differentiation affect the accessibility of the EBV genome for lytic gene expression (2,3). Another example is the proteasome inhibitor, Bortezomib, which strongly induces BZLF1 expression in latently infected tumor cells (15).…”

Deregulation of the proto-oncogene c-myc through t(8;22) translocation in Burkitt's lymphoma

“…Treatment of BL cells with sodium butyrate speci®cally downregulates transcription of the translocated c-myc gene and slightly induces P2 transcription from the normal allele (Anisimova et al, 1982;Eick et al, 1986;Polack et al, 1987Polack et al, , 1993Rottleb et al, 1995Rottleb et al, , 1996. The precise mechanism of this e ect is not known.…”