Kaposi's sarcoma-associated herpesvirus encodes a mimic of cellular miR-23

Mark Manzano*, Priscilla Shamulailatpam, Archana N. Raja, Eva Gottwein

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) expresses_20 viral microRNAs (miRNAs) in latently infected cells. We have previously shown that two of these miRNAs function as mimics of the cellular miRNAs miR-155 and miR-142-3p. Two additional KSHV miRNAs, miR-K3_1 and miR-K3, share perfect and offset 5 = homology with cellular miR-23, respectively. Here, we report a single nucleotide polymorphism that causes miR-K3_1 expression in a subset of KSHV-infected primary effusion lymphoma cell lines as a consequence of altered processing of the primary transcript by the Microprocessor complex. We confirm that miR-K3_1 regulates miR-23 targets, which is expected because these miRNAs share the entire seed region (nucleotides 2 to 8). Surprisingly, we found that miR-K3 also regulates miR-23 targets, despite offset seed sequences. In addition, the offset homology of miR-K3 to miR-23 likely allows this viral miRNA to expand its target repertoire beyond the targets of miR-23. Because miR-23 is highly expressed in endothelial cells but expressed at only low levels in B cells, we hypothesize that miR-K3 may function to introduce miR-23-like activities into KSHV-infected B cells. Together, our data demonstrate that KSHV has evolved at least three distinct viral miRNAs to tap into evolutionarily conserved cellular miRNA-regulatory networks. Furthermore, our data allow fundamental insights into the generation and functional impact of miRNA 5 = end variation.

Original languageEnglish (US)
Pages (from-to)11821-11830
Number of pages10
JournalJournal of virology
Volume87
Issue number21
DOIs
StatePublished - 2013

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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