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bioRxiv · 10.1101/660811

The oncogenic Kaposi sarcoma-associated herpesvirus encodes a mimic of the tumor suppressive miR-15/16 miRNA family

Morrison, K.·Manzano, M.·Chung, K.·Schipma, M. J.·Bartom, E. T.·Gottwein, E.
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Abstract

Many tumor viruses encode oncogenes of cellular origin. Here, we report the first instance of an oncoviral mimic of a cellular tumor suppressor. The Kaposis 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.

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Morrison, K., Manzano, M., Chung, K., Schipma, M. J., Bartom, E. T., Gottwein, E.. 2019-06-05. The oncogenic Kaposi sarcoma-associated herpesvirus encodes a mimic of the tumor suppressive miR-15/16 miRNA family. https://doi.org/10.1101/660811

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