PT - JOURNAL ARTICLE AU - Kylee Morrison AU - Mark Manzano AU - Kevin Chung AU - Matthew J. Schipma AU - Elizabeth T. Bartom AU - Eva Gottwein TI - The oncogenic Kaposi’s sarcoma-associated herpesvirus encodes a mimic of the tumor suppressive miR-15/16 miRNA family AID - 10.1101/660811 DP - 2019 Jan 01 TA - bioRxiv PG - 660811 4099 - http://biorxiv.org/content/early/2019/06/05/660811.short 4100 - http://biorxiv.org/content/early/2019/06/05/660811.full AB - Many tumor viruses encode oncogenes of cellular origin. Here, we report the first instance of an oncoviral mimic of a cellular tumor suppressor. The Kaposi’s sarcoma-associated herpesvirus (KSHV) 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 targets, including many cell cycle regulators. Inhibition of miR-K6-5p in KSHV-transformed B cells conferred a significant growth advantage. Altogether, our data show that KSHV encodes a functional mimic of the miR-15/16 miRNA family. While it is exceedingly well established that oncogenic viruses encode oncogenes of cellular origin, this is the first 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.