title: Polyomavirus BK-encoded microRNA suppresses autoregulation of viral replication.
abstract: Polyomavirus BK (BKV) infection is an important cause of renal allograft failure. Viral microRNAs are known to play a crucial role in viral replication. This study investigated the expression of BKV-encoded microRNAs (miR-B1) in patients with polyomavirus-associated nephropathy (PVAN) and their role in viral replication. Following BKV infection in renal proximal tubular cells, the 3p and 5p miR-B1 levels were significantly increased. Cells transfected with the vector containing the miR-B1 precursor (the miR-B1 vector) showed a significant increase in expression of 3p and 5p miR-B1 and decrease in luciferase activity of a reporter containing the 3p and 5p miR-B1 binding sites, compared to cells transfected with the miR-B1-mutated vector. Transfection of the miR-B1 expression vector or the 3p and 5p miR-B1 oligonucleotides inhibited expression of TAg. TAg-enhanced promoter activity and BKV replication were inhibited by miR-B1. In contrast, inhibition of miR-B1 expression by addition of miR-B1 antagomirs or silencing of Dicer upregulated the expression of TAg and VP1 proteins in BKV-infected cells. Importantly, patients with PVAN had significantly higher levels of 3p and 5p miR-B1 compared to renal transplant patients without PVAN. In conclusion, we demonstrated that (1) miR-B1 expression was upregulated during BKV infection and (2) miR-B1 suppressed TAg-mediated autoregulation of BKV replication. Use of miR-B1 can be evaluated as a potential treatment strategy against BKV infection.
authors.affiliation: Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Taipei 105, Taiwan; Department of medicine, Chang Gung University, Tao Yuan 333, Taiwan. Electronic address: dryctian@cgmh.org.tw.
authors.forename: Ya-Chung
authors.initials: YC
authors.lastname: Tian
authors.affiliation: Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Taipei 105, Taiwan; Department of medicine, Chang Gung University, Tao Yuan 333, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, 333, Taiwan.
authors.forename: Yi-Jung
authors.initials: YJ
authors.lastname: Li
authors.affiliation: Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, 333, Taiwan.
authors.forename: Hua-Chien
authors.initials: HC
authors.lastname: Chen
authors.affiliation: Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Taipei 105, Taiwan; Department of medicine, Chang Gung University, Tao Yuan 333, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, 333, Taiwan.
authors.forename: Hsin-Hsu
authors.initials: HH
authors.lastname: Wu
authors.affiliation: Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Taipei 105, Taiwan; Department of medicine, Chang Gung University, Tao Yuan 333, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, 333, Taiwan.
authors.forename: Cheng-Hao
authors.initials: CH
authors.lastname: Weng
authors.affiliation: Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Taipei 105, Taiwan; Department of medicine, Chang Gung University, Tao Yuan 333, Taiwan.
authors.forename: Yung-Chang
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Taipei 105, Taiwan; Department of medicine, Chang Gung University, Tao Yuan 333, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, 333, Taiwan.
authors.forename: Cheng-Chia
authors.initials: CC
authors.lastname: Lee
authors.affiliation: Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Taipei 105, Taiwan; Department of medicine, Chang Gung University, Tao Yuan 333, Taiwan.
authors.forename: Ming-Yang
authors.initials: MY
authors.lastname: Chang
authors.affiliation: Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Taipei 105, Taiwan; Department of medicine, Chang Gung University, Tao Yuan 333, Taiwan.
authors.forename: Hsiang-Hao
authors.initials: HH
authors.lastname: Hsu
authors.affiliation: Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Taipei 105, Taiwan; Department of medicine, Chang Gung University, Tao Yuan 333, Taiwan.
authors.forename: Tzung-Hai
authors.initials: TH
authors.lastname: Yen
authors.affiliation: Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Taipei 105, Taiwan; Department of medicine, Chang Gung University, Tao Yuan 333, Taiwan.
authors.forename: Cheng-Chieh
authors.initials: CC
authors.lastname: Hung
authors.affiliation: Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Taipei 105, Taiwan; Department of medicine, Chang Gung University, Tao Yuan 333, Taiwan.
authors.forename: Chih-Wei
authors.initials: CW
authors.lastname: Yang
mesh_terms: D000957:Antigens, Viral, Tumor / Q000235:genetics; D001739:BK Virus / Q000235:genetics / Q000502:physiology*; D036022:Capsid Proteins / Q000235:genetics; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D015967:Gene Expression Regulation, Viral; D020868:Gene Silencing; D006084:Graft Rejection / Q000821:virology*; D006706:Homeostasis; D006801:Humans; D016030:Kidney Transplantation; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D027601:Polyomavirus Infections / Q000821:virology*; D014176:Protein Biosynthesis; D012367:RNA, Viral / Q000235:genetics / Q000502:physiology*; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014779:Virus Replication
chemical_list: D000957:Antigens, Viral, Tumor; D036022:Capsid Proteins; D035683:MicroRNAs; D012367:RNA, Viral; C062481:VP1 protein, polyomavirus; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases
keywords: Autoregulation; Dicer; Large T antigen; Polyomavirus BK; microRNA