Epstein-Barr virus-encoded poly(A)- RNA supports Burkitt's lymphoma growth through interleukin-10 induction
Epstein-Barr virus-encoded poly(A)- RNA supports Burkitt's lymphoma growth through interleukin-10 induction
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DOI：
10.1093/emboj/19.24.6742
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发表时间：
2000-12-15
期刊：
影响因子：
11.4
通讯作者：
Takada, K
中科院分区：
文献类型：
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作者：
Kitagawa, N;Goto, M;Takada, K
Akata和Mutu细胞系来源于伯基特淋巴瘤（BL），并保留了EB病毒（EBV）表达的体内表型，其特征在于EBV决定的核抗原1（EBNA 1）、EBV编码的RNA（EBER）和来自BamHI A区的转录物（BARFO）的表达。我们发现，在转录水平上，EB病毒阳性Akata和Mutu细胞克隆比其EB病毒阴性亚克隆表达更高水平的白细胞介素（IL）-10。将单个EBV潜伏基因转染到EBV阴性的Akata细胞中揭示了EBER负责IL-10诱导。重组IL-10使EBV阴性Akata细胞能够在低血清（0.1%）条件下生长。另一方面，EBV阳性Akata细胞的生长通过用抗IL-10抗体或针对IL-10的反义寡核苷酸处理而被阻断，EBV阳性BL活检组织始终表达IL-10，但EBV阴性BL活检组织不表达IL-10。这些结果表明，由EBER诱导的IL-10作为BL的自分泌生长因子，EBER、EBER 1和EBER 2是非聚腺苷酸化RNA，分别为166和172个核苷酸长。目前的研究结果表明，RNA分子可以调节细胞生长。
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 nonpolyadenylated RNAs and are 166 and 172 nucleotides long, respectively. The present findings indicate that RNA molecules could regulate cell growth.