Viral microRNA targetome of KSHV-Infected primary effusion lymphoma cell lines

Eva Gottwein, David L. Corcoran, Neelanjan Mukherjee, Rebecca L. Skalsky, Markus Hafner, Jeffrey D. Nusbaum, Priscilla Shamulailatpam, Cassandra L. Love, Sandeep S. Dave, Thomas Tuschl, Uwe Ohler, Bryan R. Cullen

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208 Scopus citations

Abstract

Primary effusion lymphoma (PEL) is caused by Kaposi's sarcoma-associated herpesvirus (KSHV) and frequently also harbors Epstein-Barr virus (EBV). The expression of KSHV- and EBV-encoded microRNAs (miRNAs) in PELs suggests a role for these miRNAs in latency and lymphomagenesis. Using PAR-CLIP, a technology which allows the direct and transcriptome-wide identification of miRNA targets, we delineate the target sites for all viral and cellular miRNAs expressed in PEL cell lines. The resulting data set revealed that KSHV miRNAs directly target more than 2000 cellular mRNAs, including many involved in pathways relevant to KSHV pathogenesis. Moreover, 58% of these mRNAs are also targeted by EBV miRNAs, via distinct binding sites. In addition to a known viral analog of cellular miR-155, we show that KSHV encodes a viral miRNA that mimics cellular miR-142-3p function. In summary, this study identifies an extensive list of KSHV miRNA targets, which are likely to influence viral replication and pathogenesis.

Original languageEnglish (US)
Pages (from-to)515-526
Number of pages12
JournalCell Host and Microbe
Volume10
Issue number5
DOIs
StatePublished - Nov 17 2011

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ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

Cite this

Gottwein, E., Corcoran, D. L., Mukherjee, N., Skalsky, R. L., Hafner, M., Nusbaum, J. D., Shamulailatpam, P., Love, C. L., Dave, S. S., Tuschl, T., Ohler, U., & Cullen, B. R. (2011). Viral microRNA targetome of KSHV-Infected primary effusion lymphoma cell lines. Cell Host and Microbe, 10(5), 515-526. https://doi.org/10.1016/j.chom.2011.09.012