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Review
. 2019 Apr 15;38(8):e100941.
doi: 10.15252/embj.2018100941. Epub 2019 Mar 14.

Slicing and dicing viruses: antiviral RNA interference in mammals

Pierre V Maillard  1 , Annemarthe G van der Veen  2 , Enzo Z Poirier  2 , Caetano Reis e Sousa  3
Affiliations
Review

Slicing and dicing viruses: antiviral RNA interference in mammals

Pierre V Maillard et al. EMBO J. .

Abstract

To protect against the harmful consequences of viral infections, organisms are equipped with sophisticated antiviral mechanisms, including cell-intrinsic means to restrict viral replication and propagation. Plant and invertebrate cells utilise mostly RNA interference (RNAi), an RNA-based mechanism, for cell-intrinsic immunity to viruses while vertebrates rely on the protein-based interferon (IFN)-driven innate immune system for the same purpose. The RNAi machinery is conserved in vertebrate cells, yet whether antiviral RNAi is still active in mammals and functionally relevant to mammalian antiviral defence is intensely debated. Here, we discuss cellular and viral factors that impact on antiviral RNAi and the contexts in which this system might be at play in mammalian resistance to viral infection.

Keywords: Dicer; RNA interference; antiviral immunity; double‐stranded RNA; interferons.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1. IFN response and antiviral RNAi triggered by viral dsRNA
In the cytoplasm of mammalian cells, the RIG‐I‐like receptors (RLRs) RIG‐I and MDA5 detect viral dsRNA and trigger the production of type I interferons, which results in the induction of interferon‐stimulated genes (ISGs) that encode proteins capable of inhibiting viral replication and virus spread. In antiviral RNAi, Dicer cleaves viral dsRNA into viRNAs that are loaded into a RISC complex. As a protein component of this complex, Ago2 degrades viral RNAs with homology to the viRNAs, thereby inhibiting viral replication. RLRs and Dicer share a common DExD/H domain, composed of three helicases (Hel1, Hel2i and Hel2). RIG‐I and MDA5 additionally carry two CARD domains responsible for downstream signalling to MAVS. Dicer possesses two RNase III domains involved in dsRNA dicing.
Figure 2
Figure 2. Impact of viral and cellular determinants on antiviral RNAi
Recognition and dicing of viral dsRNA by Dicer can be influenced by various viral determinants or cellular factors, as described in main text. Known or putative mechanisms that counteract antiviral RNAi are represented with a plain or dashed red line, respectively. Structure of Dicer is based on Liu et al (2018).
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