A human torque teno virus encodes a microRNA that inhibits interferon signaling.

PLoS Pathogens
Rodney P KincaidChristopher S Sullivan

Abstract

Torque 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 tha...Continue Reading

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Datasets Mentioned

BETA
AB038624
AFL351132
AJ260231
GM19240
SRR039190
SRR039191

Methods Mentioned

BETA
transfection
transfections
PCR
Assay
chips

Software Mentioned

Mfold
Biopython
BeadStudio
gnuplot
SHRiMP2
RNAfold
Geneious
Geneious Biomatters
Image Studio
Python

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