A Human Torque Teno Virus Encodes a MicroRNA That Inhibits Interferon Signaling

dc.creatorKincaid, Rodney P.en
dc.creatorBurke, James M.en
dc.creatorCox, Jennifer C.en
dc.creatorde Villiers, Ethel-Micheleen
dc.creatorSullivan, Christopher S.en
dc.date.accessioned2014-12-15T17:10:49Zen
dc.date.available2014-12-15T17:10:49Zen
dc.date.issued2013-12-19en
dc.descriptionRodney P. Kincaid, James M. Burke, Jennifer C. Cox, Christopher S. Sullivan, The University of Texas at Austin, Molecular Genetics and Microbiology, Austin, Texas, United States of Americaen
dc.descriptionEthel-Michele de Villiers, Division for the Characterization of Tumorviruses, Deutsches Krebsforschungszentrum, Heidelberg, Germanyen
dc.description.abstractTorque teno viruses (TTVs) are a group of viruses with small, circular DNA genomes. Members of this family are thought to ubiquitously infect humans, although causal disease associations are currently lacking. At present, there is no understanding of how infection with this diverse group of viruses is so prevalent. Using a combined computational and synthetic approach, we predict and identify miRNA-coding regions in diverse human TTVs and provide evidence for TTV miRNA production in vivo. The TTV miRNAs are transcribed by RNA polymerase II, processed by Drosha and Dicer, and are active in RISC. A TTV mutant defective for miRNA production replicates as well as wild type virus genome; demonstrating that the TTV miRNA is dispensable for genome replication in a cell culture model. We demonstrate that a recombinant TTV genome is capable of expressing an exogenous miRNA, indicating the potential utility of TTV as a small RNA vector. Gene expression profiling of host cells identifies N-myc (and STAT) interactor (NMI) as a target of a TTV miRNA. NMI transcripts are directly regulated through a binding site in the 3′UTR. SiRNA knockdown of NMI contributes to a decreased response to interferon signaling. Consistent with this, we show that a TTV miRNA mediates a decreased response to IFN and increased cellular proliferation in the presence of IFN. Thus, we add Annelloviridae to the growing list of virus families that encode miRNAs, and suggest that miRNA-mediated immune evasion can contribute to the pervasiveness associated with some of these viruses.en
dc.description.catalogingnoteEmail: Chris_sullivan@mail.utexas.eduen
dc.description.departmentMolecular Biosciencesen
dc.description.departmentMicrobiologyen
dc.description.sponsorshipThis work was supported by grants RO1AI077746 from the National Institutes of Health, RP110098 from the Cancer Prevention and Research Institute of Texas, a Burroughs Wellcome Investigators in Pathogenesis Award to CSS, a UT Austin Powers Graduate Fellowship to RPK, a UT Austin Institute for Cellular and Molecular Biology fellowship, and the DKFZ for EMdV. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en
dc.identifier.Filenamejournal.ppat.1003818.pdfen
dc.identifier.citationKincaid RP, Burke JM, Cox JC, de Villiers E-M, Sullivan CS (2013) A Human Torque Teno Virus Encodes a MicroRNA That Inhibits Interferon Signaling. PLoS Pathog 9(12): e1003818. doi:10.1371/journal.ppat.1003818en
dc.identifier.doiDOI: 10.1371/journal.ppat.1003818en
dc.identifier.urihttp://hdl.handle.net/2152/27936en
dc.language.isoEnglishen
dc.publisherPLOS Pathogensen
dc.rightsAdministrative deposit of works to UT Digital Repository: This works author(s) is or was a University faculty member, student or staff member; this article is already available through open access at http://www.plospathogens.org. The public license is specified as CC-BY: http://creativecommons.org/licenses/by/4.0/. The library makes the deposit as a matter of fair use (for scholarly, educational, and research purposes), and to preserve the work and further secure public access to the works of the University.en
dc.subjectinterferonsen
dc.subjectluciferaseen
dc.subjectmicroRNAen
dc.subjectnorthern bloten
dc.subjectRNA sequense analysisen
dc.subjectRNA sequencingen
dc.subjectsmall interfering RNAen
dc.subjectviral replicationen
dc.titleA Human Torque Teno Virus Encodes a MicroRNA That Inhibits Interferon Signalingen
dc.typeArticleen

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