scholarly journals RNA Interference: Antiviral Defense Mechanism and Immune Memory

2020 ◽  
Vol 5 (2) ◽  
pp. 24
Author(s):  
Muratkhodjaev Javdat ◽  
Aripova Tamara
Keyword(s):  
Rna Interference ◽  
Defense Mechanism ◽  
Immune Memory ◽  
Antiviral Defense

scholarly journals Homologous recombination is an intrinsic defense against antiviral RNA interference

2018 ◽  
Vol 115 (39) ◽  
pp. E9211-E9219 ◽  
Author(s):  
Lauren C. Aguado ◽  
Tristan X. Jordan ◽  
Emily Hsieh ◽  
Daniel Blanco-Melo ◽  
John Heard ◽  
...  
Keyword(s):  
Rna Interference ◽  
Homologous Recombination ◽  
Virus Replication ◽  
Defense Mechanism ◽  
Selective Pressure ◽  
Rna Viruses ◽  
Antiviral Defense ◽  
Dynamic Relationship ◽  
Pathogen Prevalence ◽  
Genomic Material

RNA interference (RNAi) is the major antiviral defense mechanism of plants and invertebrates, rendering the capacity to evade it a defining factor in shaping the viral landscape. Here we sought to determine whether different virus replication strategies provided any inherent capacity to evade RNAi in the absence of an antagonist. Through the exploitation of host microRNAs, we recreated an RNAi-like environment in vertebrates and directly compared the capacity of positive- and negative-stranded RNA viruses to cope with this selective pressure. Applying this defense against four distinct viral families revealed that the capacity to undergo homologous recombination was the defining attribute that enabled evasion of this defense. Independent of gene expression strategy, positive-stranded RNA viruses that could undergo strand switching rapidly excised genomic material, while negative-stranded viruses were effectively targeted and cleared upon RNAi-based selection. These data suggest a dynamic relationship between host antiviral defenses and the biology of virus replication in shaping pathogen prevalence.

scholarly journals Regulation of the protein kinase PKR by the vaccinia virus pseudosubstrate inhibitor K3L is dependent on residues conserved between the K3L protein and the PKR substrate eIF2alpha.

1997 ◽  
Vol 17 (7) ◽  
pp. 4146-4158 ◽  
Author(s):  
M Kawagishi-Kobayashi ◽  
J B Silverman ◽  
T L Ung ◽  
T E Dever
Keyword(s):  
Protein Synthesis ◽  
Protein Kinase ◽  
Vaccinia Virus ◽  
Defense Mechanism ◽  
Mutational Analysis ◽  
Substrate Recognition ◽  
Phosphorylation Site ◽  
Antiviral Defense ◽  
Loss Of Function ◽  
Yeast Saccharomyces Cerevisiae

The mammalian double-stranded RNA-activated protein kinase PKR is a component of the cellular antiviral defense mechanism and phosphorylates Ser-51 on the alpha subunit of the translation factor eIF2 to inhibit protein synthesis. To identify the molecular determinants that specify substrate recognition by PKR, we performed a mutational analysis on the vaccinia virus K3L protein, a pseudosubstrate inhibitor of PKR. High-level expression of PKR is lethal in the yeast Saccharomyces cerevisiae because PKR phosphorylates eIF2alpha and inhibits protein synthesis. We show that coexpression of vaccinia virus K3L can suppress the growth-inhibitory effects of PKR in yeast, and using this system, we identified both loss-of-function and hyperactivating mutations in K3L. Truncation of, or point mutations within, the C-terminal portion of the K3L protein, homologous to residues 79 to 83 in eIF2alpha, abolished PKR inhibitory activity, whereas the hyperactivating mutation, K3L-H47R, increased the homology between the K3L protein and eIF2alpha adjacent to the phosphorylation site at Ser-51. Biochemical and yeast two-hybrid analyses revealed that the suppressor phenotype of the K3L mutations correlated with the affinity of the K3L protein for PKR and was inversely related to the level of eIF2alpha phosphorylation in the cell. These results support the idea that residues conserved between the pseudosubstrate K3L protein and the authentic substrate eIF2alpha play an important role in substrate recognition, and they suggest that PKR utilizes sequences both near and over 30 residues from the site of phosphorylation for substrate recognition. Finally, by reconstituting part of the mammalian antiviral defense mechanism in yeast, we have established a genetically useful system to study viral regulators of PKR.

RNA Interference Mechanisms and Applications in Plant Pathology

2018 ◽  
Vol 56 (1) ◽  
pp. 581-610 ◽  
Author(s):  
Cristina Rosa ◽  
Yen-Wen Kuo ◽  
Hada Wuriyanghan ◽  
Bryce W. Falk
Keyword(s):  
Plant Pathology ◽  
Rna Interference ◽  
Gene Function ◽  
Small Rnas ◽  
Plant Pathogens ◽  
Common Ancestor ◽  
Plant Protection ◽  
Plant Diseases ◽  
Antiviral Defense ◽  
Endogenous Genes

The origin of RNA interference (RNAi), the cell sentinel system widely shared among eukaryotes that recognizes RNAs and specifically degrades or prevents their translation in cells, is suggested to predate the last eukaryote common ancestor ( 138 ). Of particular relevance to plant pathology is that in plants, but also in some fungi, insects, and lower eukaryotes, RNAi is a primary and effective antiviral defense, and recent studies have revealed that small RNAs (sRNAs) involved in RNAi play important roles in other plant diseases, including those caused by cellular plant pathogens. Because of this, and because RNAi can be manipulated to interfere with the expression of endogenous genes in an intra- or interspecific manner, RNAi has been used as a tool in studies of gene function but also for plant protection. Here, we review the discovery of RNAi, canonical mechanisms, experimental and translational applications, and new RNA-based technologies of importance to plant pathology.

scholarly journals The Suppressor of Transgene RNA Silencing Encoded by Cucumber mosaic virus Interferes with Salicylic Acid-Mediated Virus Resistance

2001 ◽  
Vol 14 (6) ◽  
pp. 715-724 ◽  
Author(s):  
Liang-Hui Ji ◽  
Shou-Wei Ding
Keyword(s):  
Salicylic Acid ◽  
Cucumber Mosaic Virus ◽  
Mosaic Virus ◽  
Virus Resistance ◽  
Rna Silencing ◽  
Defense Mechanism ◽  
Antiviral Defense ◽  
Oxidase Gene ◽  
Systemic Spread ◽  
Systemic Infections

The Cucumber mosaic virus (CMV)-encoded 2b protein (Cmv2b) is a nuclear protein that suppresses transgene RNA silencing in Nicotiana benthamiana. Cmv2b is an important virulence determinant but nonessential for systemic spread in N. glutinosa, in contrast to its indispensable role for systemic infections in cucumber. Here, we report that Cmv2b became essential for systemic infections in older N. glutinosa plants or in young seedlings pre-treated with salicylic acid (SA). Expression of Cmv2b from the genome of either CMV or Tobacco mosaic virus significantly reduced the inhibitory effect of SA on virus accumulation in inoculated leaves and systemic leaves. A close correlation is demonstrated between Cmv2b expression and a reduced SA-dependent induction of the alternative oxidase gene, a component of the recently proposed SA-regulated antiviral defense. These results collectively reveal a novel activity of Cmv2b in the inhibition of SA-mediated virus resistance. We used a N. tabacum line expressing a bacterial nahG transgene that degrades SA to provide evidence for a Cmv2b-sensitive antiviral defense mechanism in tobacco in which SA acts as a positive modifier but not as an essential component. We propose that SA induces virus resistance by potentiating a RNA-silencing antiviral defense that is targeted by Cmv2b.

scholarly journals Computational analysis of microRNA-mediated interactions in SARS-CoV-2 infection

2020 ◽  
Author(s):  
Müşerref Duygu Saçar Demirci ◽  
Aysun Adan
Keyword(s):  
Gene Expression ◽  
Computational Analysis ◽  
Defense Mechanism ◽  
Function Analysis ◽  
Antiviral Defense ◽  
Cellular Processes ◽  
Human Mirnas ◽  
Human Genes ◽  
Viral Genes ◽  
Gene Function Analysis

AbstractMicroRNAs (miRNAs) are post-transcriptional regulators of gene expression that have been found in more than 200 diverse organisms. Although it is still not fully established if RNA viruses could generate miRNAs that would target their own genes or alter the host gene expression, there are examples of miRNAs functioning as an antiviral defense mechanism. In the case of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there are several mechanisms that would make miRNAs impact the virus, like interfering with replication, translation and even modulating the host expression. In this study, we performed a machine learning based miRNA prediction analysis for the SARS-CoV-2 genome to identify miRNA-like hairpins and searched for potential miRNA – based interactions between the viral miRNAs and human genes and human miRNAs and viral genes. Our PANTHER gene function analysis results indicate that viral derived miRNA candidates could target various human genes involved in crucial cellular processes including transcription. For instance, a transcriptional regulator, STAT1 and transcription machinery might be targeted by virus-derived miRNAs. In addition, many known human miRNAs appear to be able to target viral genes. Considering the fact that miRNA-based therapies have been successful before, comprehending mode of actions of miRNAs and their possible roles during SARS-CoV-2 infections could create new opportunities for the development and improvement of new therapeutics.

scholarly journals Endogenous RNA interference is driven by copy number

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Cristina Cruz ◽  
Jonathan Houseley
Keyword(s):  
Rna Interference ◽  
Transposable Elements ◽  
Copy Number ◽  
Defense Mechanism ◽  
Gene Copy Number ◽  
Single Copy ◽  
Gene Copy ◽  
Protein Coding ◽  
Endogenous Loci ◽  
Pervasive Transcription

A plethora of non-protein coding RNAs are produced throughout eukaryotic genomes, many of which are transcribed antisense to protein-coding genes and could potentially instigate RNA interference (RNAi) responses. Here we have used a synthetic RNAi system to show that gene copy number is a key factor controlling RNAi for transcripts from endogenous loci, since transcripts from multi-copy loci form double stranded RNA more efficiently than transcripts from equivalently expressed single-copy loci. Selectivity towards transcripts from high-copy DNA is therefore an emergent property of a minimal RNAi system. The ability of RNAi to selectively degrade transcripts from high-copy loci would allow suppression of newly emerging transposable elements, but such a surveillance system requires transcription. We show that low-level genome-wide pervasive transcription is sufficient to instigate RNAi, and propose that pervasive transcription is part of a defense mechanism capable of directing a sequence-independent RNAi response against transposable elements amplifying within the genome.

scholarly journals High-Pressure-Sprayed Double Stranded RNA Does Not Induce RNA Interference of a Reporter Gene

2020 ◽  
Vol 11 ◽  
Author(s):  
Veli Vural Uslu ◽  
Alexandra Bassler ◽  
Gabi Krczal ◽  
Michael Wassenegger
Keyword(s):  
High Pressure ◽  
Rna Interference ◽  
Reporter Gene ◽  
Plant Cell Wall ◽  
Defense Mechanism ◽  
Green Fluorescence Protein ◽  
Micro Rna ◽  
Small Rna Sequencing ◽  
Rna Molecules ◽  
Interfering Rna

In plants, RNA interference (RNAi) is an effective defense mechanism against pathogens and pests. RNAi mainly involves the micro RNA and the small interfering RNA (siRNA) pathways. The latter pathway is generally based on the processing of long double stranded RNAs (dsRNA) into siRNAs by DICER-LIKE endonucleases (DCLs). SiRNAs are loaded onto ARGONAUTE proteins to constitute the RNA-induced silencing complex (RISC). Natural dsRNAs derive from transcription of inverted repeats or of specific RNA molecules that are transcribed by RNA-directed RNA polymerase 6 (RDR6). Moreover, replication of infecting viruses/viroids results in the production of dsRNA intermediates that can serve as substrates for DCLs. The high effectiveness of RNAi both locally and systemically implicated that plants could become resistant to pathogens, including viruses, through artificial activation of RNAi by topical exogenous application of dsRNA. The most preferable procedure to exploit RNAi would be to simply spray naked dsRNAs onto mature plants that are specific for the attacking pathogens serving as a substitute for pesticides applications. However, the plant cell wall is a difficult barrier to overcome and only few reports claim that topical application of naked dsRNA triggers RNAi in plants. Using a transgenic Nicotiana benthamiana line, we found that high-pressure-sprayed naked dsRNA did not induce silencing of a green fluorescence protein (GFP) reporter gene. Small RNA sequencing (sRNA-seq) of the samples from dsRNA sprayed leaves revealed that the dsRNA was, if at all, not efficiently processed into siRNAs indicating that the dsRNA was insufficiently taken up by plant cells.

The Interplay Between Viruses and RNAi Pathways in Insects

2021 ◽  
Vol 66 (1) ◽  
pp. 61-79
Author(s):  
Bryony C. Bonning ◽  
Maria-Carla Saleh
Keyword(s):  
Small Interfering Rna ◽  
Host Response ◽  
Defense Mechanism ◽  
Antiviral Defense ◽  
Practical Application ◽  
Expression Systems ◽  
Dna Viruses ◽  
Interfering Rna ◽  
Sirna Pathway

As an overarching immune mechanism, RNA interference (RNAi) displays pathogen specificity and memory via different pathways. The small interfering RNA (siRNA) pathway is the primary antiviral defense mechanism against RNA viruses of insects and plays a lesser role in defense against DNA viruses. Reflecting the pivotal role of the siRNA pathway in virus selection, different virus families have independently evolved unique strategies to counter this host response, including protein-mediated, decoy RNA–based, and microRNA-based strategies. In this review, we outline the interplay between insect viruses and the different pathways of the RNAi antiviral response; describe practical application of these interactions for improved expression systems and for pest and disease management; and highlight research avenues for advancement of the field.

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