The Oncogenic Kaposi's Sarcoma-Associated Herpesvirus Encodes a Mimic of the Tumor-Suppressive miR-15/16 miRNA Family

Cell Rep. 2019 Dec 3;29(10):2961-2969.e6. doi: 10.1016/j.celrep.2019.11.005.


Many tumor viruses encode oncogenes of cellular origin. Here, we report an oncoviral mimic of a cellular tumor suppressor. The Kaposi's sarcoma-associated herpesvirus (KSHV) microRNA (miRNA) miR-K6-5p shares sequence similarity to the tumor-suppressive cellular miR-15/16 miRNA family. We show that miR-K6-5p inhibits cell cycle progression, a hallmark function of miR-16. miR-K6-5p regulates conserved miR-15/16 family miRNA targets, including many cell cycle regulators. Inhibition of miR-K6-5p in KSHV-transformed B cells confers a significant growth advantage. Altogether, our data show that KSHV encodes a functional mimic of miR-15/16 family miRNAs. While it is exceedingly well established that oncogenic viruses encode oncogenes of cellular origin, this is an unusual example of an oncogenic virus that encodes a viral mimic of a cellular tumor suppressor. Encoding a tumor-suppressive miRNA could help KSHV balance viral oncogene expression and thereby avoid severe pathogenesis in the healthy host.

Keywords: KSHV; miR-15/16; microRNA; tumor virus.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • B-Lymphocytes / physiology
  • B-Lymphocytes / virology
  • Carcinogenesis / genetics*
  • Cell Line
  • HEK293 Cells
  • Herpesvirus 8, Human / genetics*
  • Host-Pathogen Interactions / genetics
  • Humans
  • MicroRNAs / genetics*
  • Oncogenes / genetics*
  • RNA, Viral / genetics
  • Sarcoma, Kaposi / genetics*
  • Sarcoma, Kaposi / virology


  • MIRN15 microRNA, human
  • MIRN16 microRNA, human
  • MicroRNAs
  • RNA, Viral