Format

Send to

Choose Destination
See comment in PubMed Commons below
Biochem Biophys Res Commun. 2014 May 9;447(3):543-9. doi: 10.1016/j.bbrc.2014.04.030. Epub 2014 Apr 13.

Polyomavirus BK-encoded microRNA suppresses autoregulation of viral replication.

Author information

1
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.
2
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.
3
Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, 333, Taiwan.
4
Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Taipei 105, Taiwan; Department of medicine, Chang Gung University, Tao Yuan 333, Taiwan.

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.

KEYWORDS:

Autoregulation; Dicer; Large T antigen; Polyomavirus BK; microRNA

PMID:
24735545
DOI:
10.1016/j.bbrc.2014.04.030
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center