Marek's disease virus microRNA designated Mdv1-pre-miR-M4 targets both cellular and viral genes

Arch Virol. 2010 Nov;155(11):1823-37. doi: 10.1007/s00705-010-0777-y. Epub 2010 Aug 1.

Abstract

Mdv1-miR-M4 is one of 25 microRNAs (miRNAs) expressed by Marek's disease virus (MDV-1), an oncogenic alphaherpesvirus that induces fatal T-cell lymphoma in chickens. Mdv1-miR-M4 was shown to be the second functional viral ortholog of miR-155, a cellular miRNA that plays a crucial role in several physiological and pathological processes in lymphocyte biology. In this study, we investigated a panel of putative mdv1-miR-M4 targets involved in gene networks affecting both cellular and viral life cycles. Using luciferase reporter assays, we showed that mdv1-miR-M4-5P and miR-155 efficiently targeted a common set of 3' untranslated regions (3'UTR) of six cellular genes (GPM6B, RREB1, c-Myb, MAP3K7IP2, PU.1 and C/EBP). In addition, we also investigated the interactions between mdv1-miR-M4-5P and mdv1-miR-M43P and viral mRNAs encoding UL28 and UL32 in both reporter and western blot assays. Mdv1-miR-M4 specifically inhibited the translation of these two viral proteins, which are involved in the cleavage/packaging of herpesvirus DNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • Chickens
  • Fibroblasts / metabolism*
  • Gene Expression Regulation / physiology*
  • Leukocytes / metabolism
  • Mardivirus / genetics*
  • Mardivirus / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*

Substances

  • MicroRNAs