Cullen, BR. Is RNA interference involved in intrinsic antiviral immunity in mammals? Nat Immunol 7: 563-567

Center for Virology and Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Nature Immunology (Impact Factor: 20). 07/2006; 7(6):563-7. DOI: 10.1038/ni1352
Source: PubMed


RNA interference constitutes a key component of the innate immune response to viral infection in both plants and invertebrate animals and has been postulated to have a similar protective function in mammals. This perspective reviews the available data addressing whether RNA interference forms part of the mammalian innate immune response and concludes that the popular hypothesis in favor of that possibility remains far from proven and may not be valid.

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    • "Thus, it is widely accepted that RNAi is an antiviral response in some eukaryotes. However, in mammalian cells, the antiviral role of RNAi remains controversial (Cullen, 2006; de Vries and Berkhout, 2008; Jeang, 2012; Umbach and Cullen, 2009). There are reports that mammalian cells defective for RNAi components are more susceptible to viral replication. "
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    ABSTRACT: RNA interference (RNAi) is an established antiviral defense mechanism in plants and invertebrates. Whether RNAi serves a similar function in mammalian cells remains unresolved. We find that in some cell types, mammalian RNAi activity is reduced shortly after viral infection via poly-ADP-ribosylation of the RNA-induced silencing complex (RISC), a core component of RNAi. Well-established antiviral signaling pathways, including RIG-I/MAVS and RNaseL, contribute to inhibition of RISC. In the absence of virus infection, microRNAs repress interferon-stimulated genes (ISGs) associated with cell death and proliferation, thus maintaining homeostasis. Upon detection of intracellular pathogen-associated molecular patterns, RISC activity decreases, contributing to increased expression of ISGs. Our results suggest that, unlike in lower eukaryotes, mammalian RISC is not antiviral in some contexts, but rather RISC has been co-opted to negatively regulate toxic host antiviral effectors via microRNAs.
    Cell host & microbe 09/2013; 14(4). DOI:10.1016/j.chom.2013.09.002 · 12.33 Impact Factor
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    • "Approximately 21-nt small interfering RNAs (siRNAs) processed from viral double-stranded RNAs (dsRNAs) form the basis of antiviral immunity in plants, nematodes, and insects (Ding 2010), where they guide the endonucleolytic destruction of complementary viral RNAs in a process called RNA interference (RNAi). In contrast, RNAi is not thought to operate as an antiviral defense mechanism in mammals (Cullen 2006a). Small silencing RNAs expressed by mammals include the large family of microRNAs (miRNAs) and the less understood endogenous siRNAs (endo-siRNAs), which both associate with the Ago subfamily of Argonaute proteins. "
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    ABSTRACT: MicroRNAs (miRNAs) are a class of small noncoding RNAs expressed by plants, animals, and some viruses. miRNAs generally function as part of miRNA-induced silencing complexes to modestly repress mRNAs with imperfect sequence complementarity. Over the last years, many different roles of miRNA mediated regulation in the life cycles of mammalian viruses have been uncovered. In this chapter, I will mainly explore four different examples of how cellular miRNAs interact with viruses: the role of miR-155 in viral oncogenesis, viral strategies to eliminate cellular miR-27, the contribution of miR-122 to the replication of hepatitis C virus, and miRNAs as an experimental tool to control virus replication and vector transgene expression. In the final part of this chapter, I will give a brief overview of virally encoded microRNAs.
    Current topics in microbiology and immunology 05/2013; 371:201-227. DOI:10.1007/978-3-642-37765-5_8 · 4.10 Impact Factor
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    • "Viruses, on the other hand, produce viral suppressors of RNA silencing (VSRs) to counteract viRNAs [41]. There has been controversy regarding whether a similar antiviral mechanism might exist in mammalian cells [42] [43]. Although anti-viral siRNAs have not been documented in mammalian cells [44] [45], several virus-derived miRNAs have been identified in mammalian cells infected with the herpes virus family, such as Epstein-Barr virus (EBV) [44], Kaposi sarcoma-associated virus (KSHV) [45], and cytomegalovirus (CMV) [45] [46], as well as simian virus 4 (SV40) [47] and HIV-1 [48] [49] [50]. "
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