The Mammalian Response to Virus Infection Is Independent of Small RNA Silencing

Simone Backes, Ryan A. Langlois, Sonja Schmid, Andrew Varble, Jaehee V. Shim, David Sachs, Benjamin R. tenOever

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

A successful cellular response to virus infection is essential for evolutionary survival. In plants, arthropods, and nematodes, cellular antiviral defenses rely on RNAi. Interestingly, the mammalian response to virus is predominantly orchestrated through interferon (IFN)-mediated induction of antiviral proteins. Despite the potency of the IFN system, it remains unclear whether mammals also have the capacity to employ antiviral RNAi. Here, we investigated this by disabling IFN function, small RNA function, or both activities in the context of virus infection. We find that loss of small RNAs in the context of an invivo RNA virus infection lowers titers due to reduced transcriptional repression of the host antiviral response. In contrast, enabling a virus with the capacity to inhibit the IFN system results in increased titers. Taken together, these results indicate that small RNA silencing is not a physiological contributor to the IFN-mediated cellular response to virus infection.

Original languageEnglish (US)
Pages (from-to)114-125
Number of pages12
JournalCell reports
Volume8
Issue number1
DOIs
StatePublished - Jul 10 2014

Bibliographical note

Funding Information:
We acknowledge the Mount Sinai Genomics Core Facility for deep-sequencing analyses. This material is based upon work supported in part by the U.S. Army Research Laboratory and the U.S. Army Research Office under grant numbers W911NF-12-R-0012 and W911NF-07-R-0003. S.B. is supported by Deutsche Forschungsgemeinschaft DFG BA 4878/1-1. R.A.L. is supported by the Research Training Program in Molecular and Cellular Hematology (T32-HL094283). B.R.tO is supported in part through a Burroughs Wellcome Fund for Investigators in the Pathogenesis of Infectious Disease.

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