Polyomavirus BK-encoded microRNA suppresses autoregulation of viral replication

Biochem Biophys Res Commun. 2014 May 9;447(3):543-9. doi: 10.1016/j.bbrc.2014.04.030. Epub 2014 Apr 13.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Viral, Tumor / genetics
  • BK Virus / genetics
  • BK Virus / physiology*
  • Capsid Proteins / genetics
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism
  • Down-Regulation
  • Gene Expression Regulation, Viral
  • Gene Silencing
  • Graft Rejection / virology*
  • Homeostasis
  • Humans
  • Kidney Transplantation*
  • MicroRNAs / genetics
  • MicroRNAs / physiology*
  • Polyomavirus Infections / virology*
  • Protein Biosynthesis
  • RNA, Viral / genetics
  • RNA, Viral / physiology*
  • Ribonuclease III / genetics
  • Ribonuclease III / metabolism
  • Transcription, Genetic
  • Virus Replication*

Substances

  • Antigens, Viral, Tumor
  • Capsid Proteins
  • MicroRNAs
  • RNA, Viral
  • VP1 protein, polyomavirus
  • DICER1 protein, human
  • Ribonuclease III
  • DEAD-box RNA Helicases