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

Kylee Morrison, Mark Manzano, Kevin Chung, Matthew J. Schipma, Elizabeth T. Bartom, Eva Gottwein*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2961-2969.e6
JournalCell reports
Volume29
Issue number10
DOIs
Publication statusPublished - Dec 3 2019

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Keywords

  • KSHV
  • microRNA
  • miR-15/16
  • tumor virus

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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