Induction and Suppression of RNA Silencing by an Animal Virus

Li, Hongwei; Li, Wan Xiang; Ding, Shou‐Wei

doi:10.1126/science.1070948

Cited by 748 publications

(725 citation statements)

References 21 publications

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“…FHV with mutations in b2, a protein that shares genomic organization but not sequence similarity with a plant viral inhibitor of silencing (cucumovirus 2B), can be rescued by suppression of the RNAi pathway in animal cells. Interestingly, FHV b2 also suppresses RNA-induced silencing mechanism in plants, highlighting the conservation of RNAi pathways across kingdoms [38].…”

Section: Natural Origins Of Dsrnamentioning

confidence: 99%

RNAi: an ever-growing puzzle

Denli

Hannon

2003

Trends in Biochemical Sciences

270

167

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Section: Natural Origins Of Dsrnamentioning

confidence: 99%

RNAi: an ever-growing puzzle

Denli

Hannon

2003

Trends in Biochemical Sciences

270

167

View full text Add to dashboard Cite

“…2,16,17 The first demonstrations that RNAi acted against viruses were performed in plant systems and then recently in Drosophila. 23 Based on these studies, it has become clear that siRNAs maybe useful in developing molecular therapeutics for human viral pathogens.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of HIV-1 fusion with small interfering RNAs targeting the chemokine coreceptor CXCR4

et al. 2004

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RNA interference (RNAi) is an evolutionarily conserved process by which plants and animals protect their genomes utilizing small, double-stranded RNAs to degrade target RNAs in a sequence-specific manner. Post-transcriptional gene silencing by these moieties can lead to degradation of both cellular and viral RNAs. It has recently been shown that double-stranded, small interfering RNAs (siRNAs) of 21-25 nucleotides can be transfected into relevant cells to target specific RNAs. This approach was utilized to inhibit human immunodeficiency virus type I (HIV-1) infection in human cells. siRNAs with homology to a motif in the mRNA that encodes for the HIV-1 chemokine coreceptor CXCR4 was utilized. Complementary studies via immunofluorescence microscopy and fluorescence-activated cell sorting demonstrated downregulation of CXCR4 from the surface of cells transfected with the specific siRNAs. As well, siRNAs without sequence homology to CXCR4 were used as controls and demonstrated no downregulation of CXCR4. siRNAs targeted to another chemokine coreceptor, APJ, showed specificity for downregulation of APJ but had no effects on CXCR4.Transfections with siRNAs targeting CXCR4 mRNA were shown to inhibit HIV-1 envelope fusion, which is relatively resistant to most viral inhibitors targeting chemokine coreceptors. The specificity of this effect was demonstrated by the inhibition of fusion by CXCR4-tropic and dual-tropic (CXCR4 and CCR5) envelope glycoproteins from HIV-1 on CXCR4+ indicator cells, but the lack of effects by siRNAs targeting CXCR4 mRNA on dual-tropic HIV-1 envelopes in CCR5+ indicator cells utilizing these fusion assays. Interestingly, siRNAs targeting CXCR4 selectively inhibited CXCR4-tropic cell-free virus infection of human cells but at only modest levels as compared to cell:cell fusion. siRNA may be a potential molecular therapeutic approach to alter a cellular cofactor critical for infection of human cells by relevant strains of HIV-1. The targeting of a cellular cofactor, rather than the HIV-1-specific mRNAs or genomic RNA, holds promise as the rapid mutational ability of the HIV-1 genome may obviate the potential clinical use of RNAi directly against this virus.

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“…The siRNA corresponded specifically to FHV RNA1, supporting that siRNA opposes the accumulation of FHV RNAs. Additionally, siRNA quantities detected post-infection in Drosophila S2 cells has been shown to correlate with the quantity of dsRNA introduced to the cells [49,89]. It is postulated Dicer-2 and R2D2 are bound to the double-stranded siRNAs, to direct them to the RISC effector [125].…”

Section: Function In Invertebrate Immune Systemsmentioning

confidence: 99%

Diversity, evolution, and therapeutic applications of small RNAs in prokaryotic and eukaryotic immune systems

Cooper

Overstreet

2014

Physics of Life Reviews

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Recent evidence supports that prokaryotes exhibit adaptive immunity in the form of CRISPR (Clustered Regularly Interspersed Short Palindromic Repeats) and Cas (CRISPR associated proteins). The CRISPR-Cas system confers resistance to exogenous genetic elements such as phages and plasmids by allowing for the recognition and silencing of these genetic elements. Moreover, CRISPR-Cas serves as a memory of past exposures. This suggests that the evolution of the immune system has counterparts among the prokaryotes, not exclusively among eukaryotes. Mathematical models have been proposed which simulate the evolutionary patterns of CRISPR, however large gaps in our understanding of CRISPR-Cas function and evolution still exist. The CRISPR-Cas system is analogous to small RNAs involved in resistance mechanisms throughout the tree of life, and a deeper understanding of the evolution of small RNA pathways is necessary before the relationship between these convergent systems is to be determined. Presented in this review are novel RNAi therapies based on CRISPR-Cas analogs and the potential for future therapies based on CRISPR-Cas system components.

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Induction and Suppression of RNA Silencing by an Animal Virus

Cited by 748 publications

References 21 publications

RNAi: an ever-growing puzzle

RNAi: an ever-growing puzzle

Inhibition of HIV-1 fusion with small interfering RNAs targeting the chemokine coreceptor CXCR4

Diversity, evolution, and therapeutic applications of small RNAs in prokaryotic and eukaryotic immune systems

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