Tohoku J. Exp. Med., 2015 October, 237(2)

Profiling of EBV-Encoded microRNAs in EBV-Associated Hemophagocytic Lymphohistiocytosis

CHEN ZHOU,¹ ZHENGDE XIE,¹ LIWEI GAO,¹ CHUNYAN LIU,¹ JUNHONG AI,¹ LI ZHANG² and KUNLING SHEN¹

¹Virology Laboratory, Capital Medical University Affiliated Beijing Children's Hospital, Beijing, China
²Department of Haematology, Capital Medical University Affiliated Beijing Children's Hospital, Beijing, China

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.

keywords —— biomarker; children; Epstein-Barr virus; hemophagocytic lymphohistiocytosis; microRNA

© 2015 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2015, 237, 117-126

Correspondence: Kunling Shen, Virology Laboratory, Capital Medical University Affiliated Beijing Children's Hospital, No.56 Nanlishi Road, Xicheng District, Beijing 100045, China.

e-mail: kunlingshen1717@126.com