scholarly journals Mutation Rates, Mutation Frequencies, and Proofreading-Repair Activities in RNA Virus Genetics

Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1882 ◽  
Author(s):  
Esteban Domingo ◽  
Carlos García-Crespo ◽  
Rebeca Lobo-Vega ◽  
Celia Perales
Keyword(s):  
Error Rate ◽  
Rna Virus ◽  
Error Rates ◽  
Viral Rna ◽  
Mutation Rates ◽  
Relevant Parameter ◽  
Dna Viruses ◽  
Biologically Relevant ◽  
Host Interactions ◽  
The Stability

The error rate displayed during template copying to produce viral RNA progeny is a biologically relevant parameter of the replication complexes of viruses. It has consequences for virus–host interactions, and it represents the first step in the diversification of viruses in nature. Measurements during infections and with purified viral polymerases indicate that mutation rates for RNA viruses are in the range of 10−3 to 10−6 copying errors per nucleotide incorporated into the nascent RNA product. Although viruses are thought to exploit high error rates for adaptation to changing environments, some of them possess misincorporation correcting activities. One of them is a proofreading-repair 3′ to 5′ exonuclease present in coronaviruses that may decrease the error rate during replication. Here we review experimental evidence and models of information maintenance that explain why elevated mutation rates have been preserved during the evolution of RNA (and some DNA) viruses. The models also offer an interpretation of why error correction mechanisms have evolved to maintain the stability of genetic information carried out by large viral RNA genomes such as the coronaviruses.

scholarly journals Epitranscriptomic(N6-methyladenosine) Modification of Viral RNA and Virus-Host Interactions

2020 ◽  
Vol 10 ◽  
Author(s):  
Hasan Imam ◽  
Geon-Woo Kim ◽  
Aleem Siddiqui
Keyword(s):  
Rna Folding ◽  
Rna Stability ◽  
Viral Pathogenesis ◽  
Rna Degradation ◽  
Viral Rna ◽  
Reversible Process ◽  
Dna Viruses ◽  
Host Interactions ◽  
Novel Approaches

N6-methyladenosine (m6A) is the most prevalent and internal modification of eukaryotic mRNA. Multiple m6A methylation sites have been identified in the viral RNA genome and transcripts of DNA viruses in recent years. m6A modification is involved in all the phases of RNA metabolism, including RNA stability, splicing, nuclear exporting, RNA folding, translational modulation, and RNA degradation. Three protein groups, methyltransferases (m6A-writers), demethylases (m6A-erasers), and m6A-binding proteins (m6A-readers) regulate this dynamic reversible process. Here, we have reviewed the role of m6A modification dictating viral replication, morphogenesis, life cycle, and its contribution to disease progression. A better understanding of the m6A methylation process during viral pathogenesis is required to reveal novel approaches to combat the virus-associated diseases.

scholarly journals Purification of the Cucumber Necrosis Virus Replicase from Yeast Cells: Role of Coexpressed Viral RNA in Stimulation of Replicase Activity

2004 ◽  
Vol 78 (15) ◽  
pp. 8254-8263 ◽  
Author(s):  
Zivile Panaviene ◽  
Tadas Panavas ◽  
Saulius Serva ◽  
Peter D. Nagy
Keyword(s):  
De Novo ◽  
Rna Virus ◽  
Rna Replication ◽  
Viral Rna ◽  
Yeast Cells ◽  
Highly Active ◽  
Replicase Complex ◽  
Internal Initiation ◽  
The Stability

ABSTRACT Purified recombinant viral replicases are useful for studying the mechanism of viral RNA replication in vitro. In this work, we obtained a highly active template-dependent replicase complex for Cucumber necrosis tombusvirus (CNV), which is a plus-stranded RNA virus, from Saccharomyces cerevisiae. The recombinant CNV replicase showed properties similar to those of the plant-derived CNV replicase (P. D. Nagy and J. Pogany, Virology 276:279-288, 2000), including the ability (i) to initiate cRNA synthesis de novo on both plus- and minus-stranded templates, (ii) to generate replicase products that are shorter than full length by internal initiation, and (iii) to perform primer extension from the 3′ end of the template. We also found that isolation of functional replicase required the coexpression of the CNV p92 RNA-dependent RNA polymerase and the auxiliary p33 protein in yeast. Moreover, coexpression of a viral RNA template with the replicase proteins in yeast increased the activity of the purified CNV replicase by 40-fold, suggesting that the viral RNA might promote the assembly of the replicase complex and/or that the RNA increases the stability of the replicase. In summary, this paper reports the first purified recombinant tombusvirus replicase showing high activity and template dependence, a finding that will greatly facilitate future studies on RNA replication in vitro.

scholarly journals RNA virus-encoded microRNAs: biogenesis, functions and perspectives on application

ExRNA ◽  
2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Shoubin Zhan ◽  
Yanbo Wang ◽  
Xi Chen
Keyword(s):  
Current Knowledge ◽  
Rna Virus ◽  
Noncoding Rnas ◽  
Biological Functions ◽  
Dna Viruses ◽  
Regulate Gene Expression ◽  
Host Interactions ◽  
Small Noncoding Rnas ◽  
Genome Wide ◽  
Posttranscriptional Level

Abstract MicroRNAs (miRNAs) are small, noncoding RNAs that regulate gene expression at the posttranscriptional level and play a crucial role in development and many diseases. The discovery of miRNAs has greatly expanded our understanding of the intricate scenario of genome-wide regulation. Over the last two decades, hundreds of virus-encoded miRNAs have been identified, most of which are from DNA viruses. Although the number of reported RNA virus-derived miRNAs is increasing, current knowledge of their roles in physiological and pathological processes has remained lacking. In this review, we discuss the biogenesis and biological functions of RNA virus- encoded miRNAs and their proposed roles in virus-host interactions and further underscore their potential value in the diagnosis and treatment of viral diseases.

scholarly journals Studies on the Mechanism of Interferon Action

1970 ◽  
Vol 56 (1) ◽  
pp. 149-171 ◽  
Author(s):  
Robert M. Friedman
Keyword(s):  
Protein Synthesis ◽  
Genetic Information ◽  
Rna Synthesis ◽  
Rna Virus ◽  
Viral Rna ◽  
Virus Protein ◽  
Dna Viruses ◽  
Virus Growth ◽  
Rna And Protein Synthesis ◽  
Main Action

Interferon does not inactivate viruses or viral RNA. Virus growth is inhibited in interferon-treated cells, but apart from conferring resistance to virus growth, no other effect of interferon on cells has been definitely shown to take place. Interferon binds to cells even in the cold, but a period of incubation at 37°C is required for development of antiviral activity. Cytoplasmic uptake of interferon has not been unequivocally demonstrated. Studies with antimetabolites indicate that the antiviral action of interferon requires host RNA and protein synthesis. Experiments with 2-mercapto-1(ß-4-pyridethyl) benzimidazole (MPB) suggest that an additional step is required between the binding and the synthesis of macromolecules. Interferon does not affect the adsorption, penetration, or uncoating of RNA or DNA viruses, but viral RNA synthesis is inhibited in cells infected with RNA viruses. The main action of interferon appears to be the inhibition of the translation of virus genetic information probably by inhibiting the initiation of virus protein synthesis.

Perceptual Characteristics of Consonant Production in Apraxia of Speech and Aphasia

2019 ◽  
Vol 28 (4) ◽  
pp. 1411-1431 ◽  
Author(s):  
Lauren Bislick ◽  
William D. Hula
Keyword(s):  
Error Rate ◽  
Error Rates ◽  
Group Differences ◽  
Diagnostic Process ◽  
Apraxia Of Speech ◽  
Contextual Variables ◽  
Error Type ◽  
Type Distribution ◽  
Phonetic Features ◽  
Syllable Position

Purpose This retrospective analysis examined group differences in error rate across 4 contextual variables (clusters vs. singletons, syllable position, number of syllables, and articulatory phonetic features) in adults with apraxia of speech (AOS) and adults with aphasia only. Group differences in the distribution of error type across contextual variables were also examined. Method Ten individuals with acquired AOS and aphasia and 11 individuals with aphasia participated in this study. In the context of a 2-group experimental design, the influence of 4 contextual variables on error rate and error type distribution was examined via repetition of 29 multisyllabic words. Error rates were analyzed using Bayesian methods, whereas distribution of error type was examined via descriptive statistics. Results There were 4 findings of robust differences between the 2 groups. These differences were found for syllable position, number of syllables, manner of articulation, and voicing. Group differences were less robust for clusters versus singletons and place of articulation. Results of error type distribution show a high proportion of distortion and substitution errors in speakers with AOS and a high proportion of substitution and omission errors in speakers with aphasia. Conclusion Findings add to the continued effort to improve the understanding and assessment of AOS and aphasia. Several contextual variables more consistently influenced breakdown in participants with AOS compared to participants with aphasia and should be considered during the diagnostic process. Supplemental Material https://doi.org/10.23641/asha.9701690

The Latin Square Task as a Measure of Relational Reasoning

2020 ◽  
Vol 36 (2) ◽  
pp. 296-302 ◽  
Author(s):  
Luke J. Hearne ◽  
Damian P. Birney ◽  
Luca Cocchi ◽  
Jason B. Mattingley
Keyword(s):  
Brain Imaging ◽  
Response Times ◽  
Latin Square ◽  
Error Rates ◽  
Functional Brain Imaging ◽  
Inspection Time ◽  
Relational Reasoning ◽  
Validity And Reliability ◽  
The Stability ◽  
Test Retest Reliability

Abstract. The Latin Square Task (LST) is a relational reasoning paradigm developed by Birney, Halford, and Andrews (2006) . Previous work has shown that the LST elicits typical reasoning complexity effects, such that increases in complexity are associated with decrements in task accuracy and increases in response times. Here we modified the LST for use in functional brain imaging experiments, in which presentation durations must be strictly controlled, and assessed its validity and reliability. Modifications included presenting the components within each trial serially, such that the reasoning and response periods were separated. In addition, the inspection time for each LST problem was constrained to five seconds. We replicated previous findings of higher error rates and slower response times with increasing relational complexity and observed relatively large effect sizes (η2p > 0.70, r > .50). Moreover, measures of internal consistency and test-retest reliability confirmed the stability of the LST within and across separate testing sessions. Interestingly, we found that limiting the inspection time for individual problems in the LST had little effect on accuracy relative to the unconstrained times used in previous work, a finding that is important for future brain imaging experiments aimed at investigating the neural correlates of relational reasoning.

Correction: “Influence of Selection Bias on the Test Decision – A Simulation Study”

2014 ◽  
Vol 53 (05) ◽  
pp. 343-343
Keyword(s):  
Selection Bias ◽  
Simulation Study ◽  
Error Rate ◽  
Type I Error ◽  
Block Size ◽  
Error Rates ◽  
Type I ◽  
Type I Error Rate ◽  
Representation Error ◽  
Numeric Representation

We have to report marginal changes in the empirical type I error rates for the cut-offs 2/3 and 4/7 of Table 4, Table 5 and Table 6 of the paper “Influence of Selection Bias on the Test Decision – A Simulation Study” by M. Tamm, E. Cramer, L. N. Kennes, N. Heussen (Methods Inf Med 2012; 51: 138 –143). In a small number of cases the kind of representation of numeric values in SAS has resulted in wrong categorization due to a numeric representation error of differences. We corrected the simulation by using the round function of SAS in the calculation process with the same seeds as before. For Table 4 the value for the cut-off 2/3 changes from 0.180323 to 0.153494. For Table 5 the value for the cut-off 4/7 changes from 0.144729 to 0.139626 and the value for the cut-off 2/3 changes from 0.114885 to 0.101773. For Table 6 the value for the cut-off 4/7 changes from 0.125528 to 0.122144 and the value for the cut-off 2/3 changes from 0.099488 to 0.090828. The sentence on p. 141 “E.g. for block size 4 and q = 2/3 the type I error rate is 18% (Table 4).” has to be replaced by “E.g. for block size 4 and q = 2/3 the type I error rate is 15.3% (Table 4).”. There were only minor changes smaller than 0.03. These changes do not affect the interpretation of the results or our recommendations.

scholarly journals Two dimensionless parameters and a mechanical analogue for the HKB model of motor coordination

2021 ◽  
Author(s):  
J. F. Cass ◽  
S. J. Hogan
Keyword(s):  
Motor Coordination ◽  
Nonlinear Damping ◽  
Numerical Continuation ◽  
Arbitrary Parameter ◽  
Relevant Parameter ◽  
Coupling Coefficients ◽  
Dimensionless Parameters ◽  
Biologically Relevant ◽  
Mechanical Analogue ◽  
Partner Interaction

AbstractThe widely cited Haken–Kelso–Bunz (HKB) model of motor coordination is used in an enormous range of applications. In this paper, we show analytically that the weakly damped, weakly coupled HKB model of two oscillators depends on only two dimensionless parameters; the ratio of the linear damping coefficient and the linear coupling coefficient and the ratio of the combined nonlinear damping coefficients and the combined nonlinear coupling coefficients. We illustrate our results with a mechanical analogue. We use our analytic results to predict behaviours in arbitrary parameter regimes and show how this led us to explain and extend recent numerical continuation results of the full HKB model. The key finding is that the HKB model contains a significant amount of behaviour in biologically relevant parameter regimes not yet observed in experiments or numerical simulations. This observation has implications for the development of virtual partner interaction and the human dynamic clamp, and potentially for the HKB model itself.

scholarly journals Viruses go modular

2020 ◽  
Vol 295 (14) ◽  
pp. 4604-4616 ◽  
Author(s):  
Ariel Shepley-McTaggart ◽  
Hao Fan ◽  
Marius Sudol ◽  
Ronald N. Harty
Keyword(s):  
Hippo Pathway ◽  
Host Proteins ◽  
Dna Viruses ◽  
Ww Domain ◽  
Ww Domains ◽  
Host Interactions ◽  
New Class ◽  
Domain Interactions ◽  
Molecular Aspects ◽  
The Hippo Pathway

The WW domain is a modular protein structure that recognizes the proline-rich Pro-Pro-x-Tyr (PPxY) motif contained in specific target proteins. The compact modular nature of the WW domain makes it ideal for mediating interactions between proteins in complex networks and signaling pathways of the cell (e.g. the Hippo pathway). As a result, WW domains play key roles in a plethora of both normal and disease processes. Intriguingly, RNA and DNA viruses have evolved strategies to hijack cellular WW domain–containing proteins and thereby exploit the modular functions of these host proteins for various steps of the virus life cycle, including entry, replication, and egress. In this review, we summarize key findings in this rapidly expanding field, in which new virus-host interactions continue to be identified. Further unraveling of the molecular aspects of these crucial virus-host interactions will continue to enhance our fundamental understanding of the biology and pathogenesis of these viruses. We anticipate that additional insights into these interactions will help support strategies to develop a new class of small-molecule inhibitors of viral PPxY-host WW-domain interactions that could be used as antiviral therapeutics.

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