Epstein-Barr virus-encoded poly(A)− RNA supports Burkitt's lymphoma growth through interleukin-10 induction

• Published in: The EMBO journal Vol. 19; no. 24; pp. 6742 - 6750
• Main Authors: Kitagawa, Norihiko, Goto, Miyuki, Kurozumi, Kimikazu, Maruo, Seiji, Fukayama, Masashi, Naoe, Tomoki, Yasukawa, Masaki, Hino, Ken-ichiro, Suzuki, Toshiya, Todo, Satoru, Takada, Kenzo
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 15.12.2000; Blackwell Publishing Ltd; Oxford University Press
• Subjects: Burkitt Lymphoma - pathology; Burkitt Lymphoma - virology; Burkitt's lymphoma; Cell Division; EBV-encoded small RNA; Epstein-Barr virus; Gene Expression Regulation, Neoplastic; growth factor; Herpesvirus 4, Human - physiology; Humans; IL-10; Interleukin-10 - genetics; Lymphoma; Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Viral - genetics; Transcription, Genetic; Transfection; Tumor Cells, Cultured; Viral Proteins - genetics
• ISSN: 0261-4189; 1460-2075; 1460-2075
• DOI: 10.1093/emboj/19.24.6742

Akata and Mutu cell lines are derived from Burkitt's lymphoma (BL) and retain the in vivo phenotype of Epstein–Barr virus (EBV) expression that is characterized by expression of EBV‐determined nuclear antigen 1 (EBNA1), EBV‐encoded RNAs (EBERs) and transcripts from the BamHI A region (BARF0). We found that EBV‐positive Akata and Mutu cell clones expressed higher levels of interleukin (IL)‐10 than their EBV‐negative subclones at the transcriptional level. Transfection of an individual EBV latent gene into EBV‐negative Akata cells revealed that EBERs were responsible for IL‐10 induction. Recombinant IL‐10 enabled EBV‐negative Akata cells to grow in low (0.1%) serum conditions. On the other hand, growth of EBV‐positive Akata cells was blocked by treatment either with an anti‐IL‐10 antibody or antisense oligonucleotide against IL‐10. EBV‐positive BL biopsies consistently expressed IL‐10, but EBV‐negative BL biopsies did not. These results suggest that IL‐10 induced by EBERs acts as an autocrine growth factor for BL. EBERs, EBER1 and EBER2, are non‐polyadenylated RNAs and are 166 and 172 nucleotides long, respectively. The present findings indicate that RNA molecules could regulate cell growth.