Promiscuous expression of Epstein‐Barr virus genes in Burkitt's lymphoma from the central African country Malawi

Abstract

Primary BL in Malawian children has a very high frequency association, approaching 100%, with the human herpesvirus EBV. A detailed study carried out on viral gene expression in these tumours, using both fresh material and methanol-fixed FNAs, showed, contrary to prediction, that most belong to a variant "class II" latency category, with lytic cycle-related genes also expressed. That is, in addition to EBNA1 expression, membrane proteins (LMP1/2A), immediate early (BZLF1) and early (IR2 and IR4) genes, a putative viral oncogene (BARF1), CST (BART) antisense transcripts and the viral bcl-2 homologue are expressed in a high proportion of the BLs. Most, but not all, express the small viral (EBER) RNAs. Two other significant observations were made: (i) in addition to expression of cellular cytokine (IL-10) transcripts in all tumours investigated, the normally silent viral IL-10 homologue was expressed in some tumours; (ii) whereas EBNA1 expression from its restricted Qp promoter was generally observed, the nonrestricted Cp/Wp promoter was also active in some tumours. Viral gene expression in the Malawian [endemic (e)] BLs appears to be more promiscuous than predicted from other studies, but expression accords with the cytopathologic picture of eBLs as a rapidly proliferating cell population accompanied by considerable necrosis, and a clinically diverse disease. A small-scale study of relapse Malawian BLs revealed a different picture of viral association, more akin to systemic BL than eBL, where EBV appears to be absent or present only at very low levels. The significance of these findings is considered.

IL-10 can induce the expression of EBV-encoded latent membrane protein-1 (LMP-1) in the absence of EBNA-2 in B lymphocytes and in Burkitt lymphoma- and NK lymphoma-derived cell lines

“…53 Induction of LMP-1 by external stimuli, such as IL-10, could also partly explain the heterogeneous expression of LMP-1 in some EBV-positive B-cell malignancies 17 and the intriguing finding of scattered LMP-1-positive cells in BLs. [11][12][13][14][15] IL-10 could be produced by the malignant cells or it could be provided by the surrounding, infiltrating cells.…”

“…10 Furthermore, rare B cells expressing type II EBV latency were detected in several lymphoid malignancies, such as Burkitt lymphomas [11][12][13][14][15] and posttransplantation lymphoproliferative disease, 16,17 and in B cells of angioimmunoblastic T-cell lymphomas, 18 pleural effusion lymphomas, 19 and plasmablastic lymphomas. 20 In these conditions LMP-1 is expressed in the absence of the trans-activators EBNA-2 and EBNA-5, implying that yet unknown cellular or viral factors are responsible for its expression.…”

Measuring Epstein–Barr virus (EBV) load: the significance and application for each EBV‐associated disease

“…Although EBV latency patterns can be classified grossly into these four types, this classification is not very strict, and heterogeneous patterns are reported in EBV-associated diseases [27,28]. Patterns of viral gene expression can differ between different cell subsets in the same individual or even tissue.…”

Epstein–Barr virus gene expression in human breast cancer: protagonist or passenger?

“…For histochemical analyses, paraffin blocks were kept at À201C. Other controls used for this study included a North African NPC (C15) passaged as a xenograft in nude mice and containing 30 copies of the EBV genome (Busson et al, 1988), a primary African Burkitt's lymphoma (from Xue et al, 2002), Asian NPCs (from Hong Kong) and numerous EBV-carrying lymphocyte cell lines.…”