title: Profiling of EBV-Encoded microRNAs in EBV-Associated Hemophagocytic Lymphohistiocytosis.
abstract: 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.
authors.affiliation: Virology Laboratory, Capital Medical University Affiliated Beijing Children's Hospital.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhou
authors.forename: Zhengde
authors.initials: Z
authors.lastname: Xie
authors.forename: Liwei
authors.initials: L
authors.lastname: Gao
authors.forename: Chunyan
authors.initials: C
authors.lastname: Liu
authors.forename: Junhong
authors.initials: J
authors.lastname: Ai
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Kunling
authors.initials: K
authors.lastname: Shen
mesh_terms: D015415:Biomarkers; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000378:metabolism; D002353:Carrier State / Q000821:virology; D002648:Child; D002675:Child, Preschool; D015245:Deoxyribonuclease BamHI / Q000235:genetics; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000188:drug therapy / Q000401:mortality; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D007244:Infectious Mononucleosis / Q000821:virology; D051359:Lymphohistiocytosis, Hemophagocytic / Q000188:drug therapy / Q000209:etiology* / Q000401:mortality; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; D012367:RNA, Viral; D015245:Deoxyribonuclease BamHI