Zhou Chen, Xie Zhengde, Gao Liwei, Liu Chunyan, Ai Junhong, Zhang Li, Shen Kunling
Virology Laboratory, Capital Medical University Affiliated Beijing Children's Hospital.
Tohoku J Exp Med. 2015 Oct;237(2):117-26. doi: 10.1620/tjem.237.117.
Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a life-threatening complication of EBV infection. MicroRNAs (miRNAs) were small non-coding RNA, and EBV could encode miRNAs that are involved in the progression of infection. However, the profiles of EBV-miRNAs in EBV-HLH were unknown. Here, we aimed to profile the expression of EBV-miRNAs in children with EBV-HLH by analyzing 44 known EBV-miRNAs, encoded within the BamHI fragment H rightward open reading frame 1 (BHRF1) and the BamHI-A region rightward transcript (BART), in plasma and cellular targets by real-time quantitative PCR. The study included 15 children with EBV-HLH, 15 children with infectious mononucleosis (IM), and 15 healthy controls. CD8(+) T cells were found to be the cellular target of EBV infection in EBV-HLH, while CD19(+) B cells were infected with EBV in IM. We also found the greater levels of several miRNAs encoded by BART in EBV-HLH, compared to those in IM and healthy controls, whereas the levels of BHRF1 miRNAs were lower than those in IM. The profile and pattern of EBV-miRNAs in EBV-HLH indicated that EBV could display type II latency in EBV-HLH. Importantly, the level of plasma miR-BART16-1 continued decreasing during the whole chemotherapy, suggesting that plasma miR-BART16-1 could be a potential biomarker for monitoring EBV-HLH progression. The pathogenesis of EBV-HLH might be attributed to the abundance of EBV-miRNAs in EBV-HLH. These findings help elucidate the roles of EBV miRNAs in EBV-HLH, enabling the understanding of the basis of this disease and providing clues for its treatment.
爱泼斯坦-巴尔病毒相关噬血细胞性淋巴组织细胞增生症（EBV-HLH）是EBV感染的一种危及生命的并发症。微小RNA（miRNA）是小的非编码RNA，EBV可编码参与感染进程的miRNA。然而，EBV-HLH中EBV-miRNA的表达谱尚不清楚。在此，我们旨在通过实时定量PCR分析血浆和细胞靶点中44种已知的EBV-miRNA（由BamHI片段H右向开放阅读框1（BHRF1）和BamHI-A区域右向转录本（BART）编码），来描绘EBV-HLH患儿中EBV-miRNA的表达情况。该研究纳入了15例EBV-HLH患儿、15例传染性单核细胞增多症（IM）患儿和15名健康对照。发现CD8(+)T细胞是EBV-HLH中EBV感染的细胞靶点，而IM中CD19(+)B细胞被EBV感染。我们还发现，与IM和健康对照相比，EBV-HLH中由BART编码的几种miRNA水平更高，而BHRF1 miRNA水平低于IM。EBV-HLH中EBV-miRNA的表达谱和模式表明，EBV在EBV-HLH中可能表现为II型潜伏。重要的是，血浆miR-BART16-1水平在整个化疗过程中持续下降，这表明血浆miR-BART16-1可能是监测EBV-HLH进展的潜在生物标志物。EBV-HLH的发病机制可能归因于EBV-HLH中EBV-miRNA的丰富。这些发现有助于阐明EBV miRNA在EBV-HLH中的作用，有助于理解该疾病的基础，并为其治疗提供线索。
