title: The Mammalian response to virus infection is independent of small RNA silencing.
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 in vivo 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.
authors: Department of Microbiology, Icahn Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors: Simone
authors: S
authors: Backes
authors: Department of Microbiology, Icahn Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors: Ryan A
authors: RA
authors: Langlois
authors: Department of Microbiology, Icahn Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors: Sonja
authors: S
authors: Schmid
authors: Department of Microbiology, Icahn Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors: Andrew
authors: A
authors: Varble
authors: Department of Microbiology, Icahn Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors: Jaehee V
authors: JV
authors: Shim
authors: Department of Genetics and Genomic Sciences, Icahn Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors: David
authors: D
authors: Sachs
authors: Department of Microbiology, Icahn Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: benjamin.tenoever@mssm.edu.
authors: Benjamin R
authors: BR
authors: tenOever
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D006224:Cricetinae; D007372:Interferons / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*; D034743:RNA-Induced Silencing Complex / Q000235:genetics / Q000378:metabolism; D018353:Rhabdoviridae Infections / Q000378:metabolism*; D014709:Vero Cells; D018116:Vesiculovirus / Q000502:physiology
chemical_list: D034741:RNA, Small Interfering; D034743:RNA-Induced Silencing Complex; D007372:Interferons