MicroRNAs encoded by Kaposi's sarcoma-associated herpesvirus regulate viral life cycle

EMBO Rep. 2010 Oct;11(10):784-90. doi: 10.1038/embor.2010.132. Epub 2010 Sep 17.


Kaposi's sarcoma-associated herpesvirus (KSHV) is linked with Kaposi's sarcoma and lymphomas. The pathogenesis of KSHV depends on the balance between two phases of the viral cycle: latency and lytic replication. In this study, we report that KSHV-encoded microRNAs (miRNAs) function as regulators by maintaining viral latency and inhibiting viral lytic replication. MiRNAs are short, noncoding, small RNAs that post-transcriptionally regulate the expression of messenger RNAs. Of the 12 viral miRNAs expressed in latent KSHV-infected cells, we observed that expression of miR-K3 can suppress both viral lytic replication and gene expression. Further experiments indicate that miR-K3 can regulate viral latency by targeting nuclear factor I/B. Nuclear factor I/B can activate the promoter of the viral immediate-early transactivator replication and transcription activator (RTA), and depletion of nuclear factor I/B by short hairpin RNAs had similar effects on the viral life cycle to those of miR-K3. Our results suggest a role for KSHV miRNAs in regulating the viral life cycle.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • DNA Replication*
  • DNA, Viral / biosynthesis
  • Gene Expression Regulation, Viral
  • Herpesvirus 8, Human / genetics*
  • Herpesvirus 8, Human / physiology
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Promoter Regions, Genetic
  • RNA, Messenger / metabolism*
  • Sarcoma, Kaposi / physiopathology
  • Trans-Activators / metabolism
  • Virus Latency*
  • Virus Replication


  • DNA, Viral
  • MicroRNAs
  • RNA, Messenger
  • Trans-Activators