Polyomavirus BK-encoded microRNA suppresses autoregulation of viral replication

Ya Chung Tian*, Yi Jung Li, Hua Chien Chen, Hsin Hsu Wu, Cheng Hao Weng, Yung Chang Chen, Cheng Chia Lee, Ming Yang Chang, Hsiang Hao Hsu, Tzung Hai Yen, Cheng Chieh Hung, Chih Wei Yang

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

28 Scopus citations

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.

Original languageEnglish
Pages (from-to)543-549
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume447
Issue number3
DOIs
StatePublished - 09 05 2014

Keywords

  • Autoregulation
  • Dicer
  • Large T antigen
  • MicroRNA
  • Polyomavirus BK

Fingerprint

Dive into the research topics of 'Polyomavirus BK-encoded microRNA suppresses autoregulation of viral replication'. Together they form a unique fingerprint.

Cite this