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

Akata and Mutu cell lines are derived from Burkitt's lymphoma (BL) and reta in the in vivo phenotype of Epstein-Barr virus (EBV) expression that is cha racterized by expression of EBV-determined nuclear antigen 1 (EBNA1), EBV-e ncoded RNAs (EBERs) and transcripts from the BamHI A region (BARF0). We fou nd that EBV-positive Akata and Mutu cell clones expressed higher levels of interleukin (IL)-10 than their EBV-negative subclones at the transcriptiona l level. Transfection of an individual EBV latent gene into EBV-negative Ak ata cells revealed that EBERs were responsible for IL-10 induction. Recombi nant IL-10 enabled EBV-negative Akata cells to grow in low (0.1%) serum con ditions. On the other hand, growth of EBV-positive Akata cells was blocked by treatment either with an anti-IL-10 antibody or antisense oligonucleotid e 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 nonpolyadenylated RNAs and are 166 and 172 nucleotides long, respecti vely. The present findings indicate that RNA molecules could regulate cell growth.