Antiviral RNA interference (RNAi) is an immune pathway that can, in certain conditions, protect mammalian cells against RNA viruses. It depends on the recognition and dicing of viral double-stranded RNA by a protein of the Dicer family, which leads to the production of viral small interfering RNAs (vsiRNAs) that sequence-specifically guide the degradation of cognate viral RNA. If the first line of defence against viruses relies on type-I and type-III interferons (IFN) in mammals, certain cell types such as stem cells, that are hyporesponsive for IFN, instead use antiviral RNAi via the expression of a specific antiviral Dicer. In certain conditions, antiviral RNAi can also contribute to the protection of differentiated cells. Indeed, abundant vsiRNAs are detected in infected cells and efficiently guide the degradation of viral RNA, especially in cells infected with viruses disabled for viral suppressors of RNAi (VSRs), which are virally encoded blockers of antiviral RNAi. The existence and importance of antiviral RNAi in differentiated cells has however been debated in the field, because data document mutual inhibition between IFN and antiviral RNAi. Recent developments include the engineering of a small molecule inhibitor of VSR to probe antiviral RNAi in vivo, as well as the detection of vsiRNAs inside extracellular vesicles in the serum of infected mice. It suggests that using more complex, in vivo models could allow to unravel the contribution of antiviral RNAi to immunity at the host level.
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Cover Image
Cover Image
Macrophages are innate immune cells responsible for a variety of tissue-specific homeostatic functions and responding to infiltrating pathogens. A lot of what we know about macrophages comes from studies on unphysiological 2D plastic dishes, however new insights into macrophage biology are emerging thanks to 3D cell culture technology (see the review in this issue by Cutter et al., pages 387–401). Depicted here is a macrophage suspended within a neon 3D dimension. Image provided by Katrina Binger.
RNA interference, an emerging component of antiviral immunity in mammals
Dario Pasquale Anobile, Enzo Z. Poirier; RNA interference, an emerging component of antiviral immunity in mammals. Biochem Soc Trans 27 February 2023; 51 (1): 137–146. doi: https://doi.org/10.1042/BST20220385
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