Promiscuous expression of Epstein-Barr virus genes in Burkitt's lymphoma from the central African country Malawi.
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.
Viral Oncology Unit, Faculty of Medicine, Imperial College of Science, Technology and Medicine, London, United Kingdom.
Shao-an
SA
Xue
Louise G
LG
Labrecque
Qi-Long
QL
Lu
S Kate
SK
Ong
Irvin A
IA
Lampert
Peter
P
Kazembe
Elizabeth
E
Molyneux
Robin L
RL
Broadhead
Eric
E
Borgstein
Beverly E
BE
Griffin
D000956:Antigens, Viral / Q000032:analysis; D001707:Biopsy, Needle; D002051:Burkitt Lymphoma / Q000235:genetics / Q000821:virology*; D002648:Child; D005404:Fixatives; D015870:Gene Expression; D005814:Genes, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D016753:Interleukin-10 / Q000235:genetics; D008295:Malawi; D000432:Methanol; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000235:genetics; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014764:Viral Proteins / Q000235:genetics
D000956:Antigens, Viral; C066460:BCRF1 protein, Human herpesvirus 4; C099537:Epstein-Barr virus encoded RNA 1; D005404:Fixatives; D012333:RNA, Messenger; D012367:RNA, Viral; D014764:Viral Proteins; D016753:Interleukin-10; D000432:Methanol