Epstein-Barr virus-encoded latent membrane protein 1 (LMP1) induces the expression of the cellular microRNA miR-146a

RNA Biol. 2007 Nov;4(3):131-7. doi: 10.4161/rna.4.3.5206.


MicroRNAs (miRNAs) are involved in sequence-specific cleavage, translational repression or deadenylation of specific target mRNAs resulting in post-transcriptional gene silencing. Epstein-Barr Virus (EBV) infection induces cellular non-coding (nc)RNAs e.g., the "vault" RNAs or miRNAs such as miR-21, miR-155 or miR-146a. MiR-146a is upregulated in various tumours and plays a role in innate immunity. We show that the EBV-encoded latent membrane protein 1 (LMP1) induces the expression of miR-146a via NFkappaB. LMP1 activates the miR-146a promoter but not a promoter with a mutation of the NFkappaB-response elements. Conversely, a LMP1-mutant deficient in NFkappaB-activation failed to activate the promoter. The "CAO"-LMP1 variant which has an increased potential to induce NFkappaB also showed a higher ability to activate the miR-146a promoter as compared to standard B95.8-LMP1. Northern blotting revealed high levels of miR-146a and miR-155 in the Burkitt's lymphoma cell line Jijoye which expresses LMP1 while the LMP1-deficient P3HR1 mutant derived from Jijoye expresses less miR-146a or miR-155. Likewise, EBV-latency type I Burkitt's lymphoma cells with low LMP1 levels also contain low levels of either miR-146a or miR-155 while their levels are increased in LMP1-expressing EBV-latency type III BL cells. Expression of LMP1 in P3HR1 cells upregulates miR-146a levels. Neither miR-146a nor miR-155 are detectable in BCBL-1 cells transformed by the Kaposi-Sarcoma Herpes virus (KSHV/HHV8). It is possible that the induction of miR-146a plays a role in the induction or maintenance of EBV latency by modulating innate immune responses to the virus infected host cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / virology
  • Base Sequence
  • Burkitt Lymphoma / immunology
  • Burkitt Lymphoma / metabolism
  • Burkitt Lymphoma / virology
  • Cell Line
  • Cell Line, Transformed
  • Cell Line, Tumor
  • Gene Expression Regulation, Viral / physiology*
  • Herpesvirus 4, Human / physiology*
  • Humans
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics*
  • Molecular Sequence Data
  • NF-kappa B / physiology
  • Viral Matrix Proteins / physiology*
  • Virus Latency / genetics


  • EBV-associated membrane antigen, Epstein-Barr virus
  • MIRN146 microRNA, human
  • MicroRNAs
  • NF-kappa B
  • Viral Matrix Proteins