scholarly journals A putative antiviral role of plant cytidine deaminases

2014 ◽  
Author(s):  
Susana Martín ◽  
José M. Cuevas ◽  
Ana Grande-Pérez ◽  
Santiago F. Elena
Keyword(s):  
Mammalian Cells ◽  
Mutagenic Activity ◽  
Population Diversity ◽  
Viral Fitness ◽  
Cauliflower Mosaic Virus ◽  
Cytidine Deaminases ◽  
Viral Genomes ◽  
Lethal Mutagenesis ◽  
Model Plant Arabidopsis Thaliana ◽  
Antiviral Mechanism

A mechanism of innate antiviral immunity operating against viruses infecting mammalian cells has been described during the last decade. Host cytidine deaminases (e.g., APOBEC3 proteins) edit viral genomes giving raise to hypermutated nonfunctional viruses; consequently, viral fitness is reduced through lethal mutagenesis. By contrast, sub-lethal hypermutagenesis may contribute to virus evolvability by increasing population diversity. To prevent genome editing, some viruses have evolved proteins that mediate APOBEC3 degradation. The model plant Arabidopsis thaliana encodes for nine cytidine deaminases (AtCDAs), raising the question of whether deamination is an antiviral mechanism in plants as well. Here we tested the effects of AtCDAs expression on the pararetrovirus Cauliflower mosaic virus (CaMV). We show that A. thaliana AtCDA1 gene product exerts a mutagenic activity, which indeed generates a negative correlation between the level of AtCDA1 expression and CaMV accumulation in the plant, suggesting that deamination may also work as an antiviral mechanism in plants.

scholarly journals A putative antiviral role of plant cytidine deaminases

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 622
Author(s):  
Susana Martín ◽  
José M. Cuevas ◽  
Ana Grande-Pérez ◽  
Santiago F. Elena
Keyword(s):  
Mammalian Cells ◽  
Mutagenic Activity ◽  
Population Diversity ◽  
Viral Fitness ◽  
Cauliflower Mosaic Virus ◽  
Cytidine Deaminases ◽  
Viral Genomes ◽  
Mutational Spectra ◽  
Antiviral Mechanism

Background: A mechanism of innate antiviral immunity operating against viruses infecting mammalian cells has been described during the last decade.  Host cytidine deaminases (e.g., APOBEC3 proteins) edit viral genomes, giving rise to hypermutated nonfunctional viruses; consequently, viral fitness is reduced through lethal mutagenesis.  By contrast, sub-lethal hypermutagenesis may contribute to virus evolvability by increasing population diversity.  To prevent genome editing, some viruses have evolved proteins that mediate APOBEC3 degradation.  The model plant Arabidopsis thaliana genome encodes nine cytidine deaminases (AtCDAs), raising the question of whether deamination is an antiviral mechanism in plants as well. Methods: Here we tested the effects of expression of AtCDAs on the pararetrovirus Cauliflower mosaic virus (CaMV). Two different experiments were carried out. First, we transiently overexpressed each one of the nine A. thaliana AtCDA genes in Nicotiana bigelovii plants infected with CaMV, and characterized the resulting mutational spectra, comparing them with those generated under normal conditions.  Secondly, we created A. thaliana transgenic plants expressing an artificial microRNA designed to knock-out the expression of up to six AtCDA genes.  This and control plants were then infected with CaMV.  Virus accumulation and mutational spectra where characterized in both types of plants. Results:  We have shown that the A. thaliana AtCDA1 gene product exerts a mutagenic activity, significantly increasing the number of G to A mutations in vivo, with a concomitant reduction in the amount of CaMV genomes accumulated.  Furthermore, the magnitude of this mutagenic effect on CaMV accumulation is positively correlated with the level of AtCDA1 mRNA expression in the plant. Conclusions: Our results suggest that deamination of viral genomes may also work as an antiviral mechanism in plants.

scholarly journals A putative antiviral role of plant cytidine deaminases

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 622 ◽  
Author(s):  
Susana Martín ◽  
José M. Cuevas ◽  
Ana Grande-Pérez ◽  
Santiago F Elena
Keyword(s):  
Mammalian Cells ◽  
Mutagenic Activity ◽  
Population Diversity ◽  
Viral Fitness ◽  
Cauliflower Mosaic Virus ◽  
Cytidine Deaminases ◽  
Viral Genomes ◽  
Mutational Spectra ◽  
Antiviral Mechanism

Background: A mechanism of innate antiviral immunity operating against viruses infecting mammalian cells has been described during the last decade.  Host cytidine deaminases (e.g., APOBEC3 proteins) edit viral genomes, giving rise to hypermutated nonfunctional viruses; consequently, viral fitness is reduced through lethal mutagenesis.  By contrast, sub-lethal hypermutagenesis may contribute to virus evolvability by increasing population diversity.  To prevent genome editing, some viruses have evolved proteins that mediate APOBEC3 degradation.  The model plant Arabidopsis thaliana genome encodes nine cytidine deaminases (AtCDAs), raising the question of whether deamination is an antiviral mechanism in plants as well. Methods: Here we tested the effects of expression of AtCDAs on the pararetrovirus Cauliflower mosaic virus (CaMV). Two different experiments were carried out. First, we transiently overexpressed each one of the nine A. thaliana AtCDA genes in Nicotiana bigelovii plants infected with CaMV, and characterized the resulting mutational spectra, comparing them with those generated under normal conditions.  Secondly, we created A. thaliana transgenic plants expressing an artificial microRNA designed to knock-out the expression of up to six AtCDA genes.  This and control plants were then infected with CaMV.  Virus accumulation and mutational spectra where characterized in both types of plants. Results:  We have shown that the A. thaliana AtCDA1 gene product exerts a mutagenic activity, significantly increasing the number of G to A mutations in vivo, with a concomitant reduction in the amount of CaMV genomes accumulated.  Furthermore, the magnitude of this mutagenic effect on CaMV accumulation is positively correlated with the level of AtCDA1 mRNA expression in the plant. Conclusions: Our results suggest that deamination of viral genomes may also work as an antiviral mechanism in plants.

scholarly journals Bacteria facilitate viral co-infection of mammalian cells and promote genetic recombination

2017 ◽  
Author(s):  
A.K. Erickson ◽  
P.R. Jesudhasan ◽  
M.J. Mayer ◽  
A. Narbad ◽  
S.E. Winter ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Genetic Recombination ◽  
Enteric Viruses ◽  
Intestinal Bacteria ◽  
Enteric Virus ◽  
Viral Fitness ◽  
Host Cells ◽  
Bacterial Strains ◽  
Viral Recombination ◽  
Viral Genomes

SUMMARYIntestinal bacteria promote infection of several mammalian enteric viruses, but the mechanisms and consequences are unclear. We screened a panel of 41 bacterial strains as a platform to determine how different bacteria impact enteric viruses. We found that most bacterial strains bound poliovirus, a model enteric virus. Given that each bacterium bound multiple virions, we hypothesized that bacteria may deliver multiple viral genomes to a mammalian cell even when very few virions are present, such as during the first replication cycle after inter-host transmission. We found that exposure to certain bacterial strains increased viral co-infection even when the ratio of virus to host cells was low. Bacteria-mediated viral co-infection correlated with bacterial adherence to cells. Importantly, bacterial strains that induced viral co-infection facilitated viral fitness restoration through genetic recombination. Thus, bacteria-virus interactions may increase viral fitness through viral recombination at initial sites of infection, potentially limiting abortive infections.

scholarly journals Mycoviral Population Dynamics in Spanish Isolates of the Entomopathogenic Fungus Beauveria bassiana

Viruses ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 665 ◽  
Author(s):  
Charalampos Filippou ◽  
Inmaculada Garrido-Jurado ◽  
Nicolai Meyling ◽  
Enrique Quesada-Moraga ◽  
Robert Coutts ◽  
...  
Keyword(s):  
Beauveria Bassiana ◽  
Entomopathogenic Fungi ◽  
Insect Pests ◽  
Fruit Fly ◽  
Population Diversity ◽  
Viral Genomes ◽  
Large Panels ◽  
High Virulence ◽  
Fungus Beauveria Bassiana ◽  
Rna Polymerase Gene

The use of mycoviruses to manipulate the virulence of entomopathogenic fungi employed as biocontrol agents may lead to the development of novel methods to control attacks by insect pests. Such approaches are urgently required, as existing agrochemicals are being withdrawn from the market due to environmental and health concerns. The aim of this work is to investigate the presence and diversity of mycoviruses in large panels of entomopathogenic fungi, mostly from Spain and Denmark. In total, 151 isolates belonging to the genera Beauveria, Metarhizium, Lecanicillium, Purpureocillium, Isaria, and Paecilomyces were screened for the presence of dsRNA elements and 12 Spanish B. bassiana isolates were found to harbor mycoviruses. All identified mycoviruses belong to three previously characterised species, the officially recognised Beauveria bassiana victorivirus 1 (BbVV-1) and the proposed Beauveria bassiana partitivirus 2 (BbPV-2) and Beauveria bassiana polymycovirus 1 (BbPmV-1); individual B. bassiana isolates may harbor up to three of these mycoviruses. Notably, these mycovirus species are under distinct selection pressures, while recombination of viral genomes increases population diversity. Phylogenetic analysis of the RNA-dependent RNA polymerase gene sequences revealed that the current population structure in Spain is potentially a result of both vertical and horizontal mycovirus transmission. Finally, pathogenicity experiments using the Mediterranean fruit fly Ceratitis capitata showed no direct correlation between the presence of any particular mycovirus and the virulence of the B. bassiana isolates, but illustrated potentially interesting isolates that exhibit relatively high virulence, which will be used in more detailed virulence experimentation in the future.

scholarly journals QSAR Analysis for the Inhibition of the Mutagenic Activity by Anthocyanin Derivatives

2020 ◽  
Vol 5 (4) ◽  
pp. 69-82
Author(s):  
Nicolas Alejandro Szewczuk ◽  
Pablo Román Duchowicz ◽  
Alicia Beatriz Pomilio
Keyword(s):  
Cytochrome P450 ◽  
Mammalian Cells ◽  
Mutagenic Activity ◽  
3D Qsar ◽  
Cytochrome P450 3A4 ◽  
Linear Regression Models ◽  
Qsar Analysis ◽  
Proposed Model ◽  
Qsar Models ◽  
Cellular Dna

Flavonoid compounds modulate the cytochrome P450 3A4 enzyme activity and inhibit the mutagenic activity of mammalian cells, preventing carcinogen activation and cellular DNA damage. In this work, the quantitative structure-activity relationships (QSAR) theory is applied to predict the cytochrome P450 3A4 inhibition constant by anthocyanin derivatives. Different freely available software calculates 102,260 non-conformational molecular descriptors. A training set of 12 compounds is used to calibrate the best univariable linear regression models, while a test set of 4 compounds is used to explore their predictive capability. The present results are compared with previously reported ones by using 3D-QSAR, thus demonstrating that the proposed topological QSAR models achieve acceptable statistical quality. The proposed model provides a prospective QSAR guide for the search of new anthocyanin derivatives possessing high or low predicted mutagenicity.

scholarly journals Why viruses sometimes disperse in groups†

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Rafael Sanjuán ◽  
María-Isabel Thoulouze
Keyword(s):  
Genetic Relatedness ◽  
Lipid Vesicles ◽  
Viral Fitness ◽  
Target Cells ◽  
Spatial And Temporal Scales ◽  
Viral Genomes ◽  
Antiviral Responses ◽  
Viral Spread ◽  
Protein Matrices ◽  
Viral Components

AbstractMany organisms disperse in groups, yet this process is understudied in viruses. Recent work, however, has uncovered different types of collective infectious units, all of which lead to the joint delivery of multiple viral genome copies to target cells, favoring co-infections. Collective spread of viruses can occur through widely different mechanisms, including virion aggregation driven by specific extracellular components, cloaking inside lipid vesicles, encasement in protein matrices, or binding to cell surfaces. Cell-to-cell viral spread, which allows the transmission of individual virions in a confined environment, is yet another mode of clustered virus dissemination. Nevertheless, the selective advantages of dispersing in groups remain poorly understood in most cases. Collective dispersal might have emerged as a means of sharing efficacious viral transmission vehicles. Alternatively, increasing the cellular multiplicity of infection may confer certain short-term benefits to viruses, such as overwhelming antiviral responses, avoiding early stochastic loss of viral components required for initiating infection, or complementing genetic defects present in different viral genomes. However, increasing infection multiplicity may also entail long-term costs, such as mutation accumulation and the evolution of defective particles or other types of cheater viruses. These costs and benefits, in turn, should depend on the genetic relatedness among collective infectious unit members. Establishing the genetic basis of collective viral dispersal and performing controlled experiments to pinpoint fitness effects at different spatial and temporal scales should help us clarify the implications of these spread modes for viral fitness, pathogenicity, and evolution.

Ribavirin's antiviral mechanism of action: lethal mutagenesis?

2002 ◽  
Vol 80 (2) ◽  
pp. 86-95 ◽  
Author(s):  
Shane Crotty ◽  
Craig Cameron ◽  
Raul Andino
Keyword(s):  
Mechanism Of Action ◽  
Lethal Mutagenesis ◽  
Antiviral Mechanism

scholarly journals Oxidative Stress, Mutations and Chromosomal Aberrations Induced by In Vitro and In Vivo Exposure to Furan

2021 ◽  
Vol 22 (18) ◽  
pp. 9687
Author(s):  
Maria Teresa Russo ◽  
Gabriele De Luca ◽  
Nieves Palma ◽  
Paola Leopardi ◽  
Paolo Degan ◽  
...  
Keyword(s):  
Thermal Processing ◽  
Mammalian Cells ◽  
Mutagenic Activity ◽  
Critical Role ◽  
Dna Lesions ◽  
Sufficient Evidence ◽  
Chromosomal Damage ◽  
Vast Number

Furan is a volatile compound that is formed in foods during thermal processing. It is classified as a possible human carcinogen by international authorities based on sufficient evidence of carcinogenicity from studies in experimental animals. Although a vast number of studies both in vitro and in vivo have been performed to investigate furan genotoxicity, the results are inconsistent, and its carcinogenic mode of action remains to be clarified. Here, we address the mutagenic and clastogenic activity of furan and its prime reactive metabolite cis-2 butene-1,4-dial (BDA) in mammalian cells in culture and in mouse animal models in a search for DNA lesions responsible of these effects. To this aim, Fanconi anemia-derived human cell lines defective in the repair of DNA inter-strand crosslinks (ICLs) and Ogg1−/− mice defective in the removal of 8-hydroxyguanine from DNA, were used. We show that both furan and BDA present a weak (if any) mutagenic activity but are clear inducers of clastogenic damage. ICLs are strongly indicated as key lesions for chromosomal damage whereas oxidized base lesions are unlikely to play a critical role.

A novel method of analyzing environmental chemical mutagens in human cell systems

2000 ◽  
Vol 42 (7-8) ◽  
pp. 133-138 ◽  
Author(s):  
S. Takahashi ◽  
X. J. Chi ◽  
J. Nomura ◽  
S. Sugaya ◽  
K. Kita ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Mutagenic Activity ◽  
Peripheral Blood Lymphocytes ◽  
Environmental Chemical ◽  
Cell Systems ◽  
Low Concentrations ◽  
Cultured Human Cells ◽  
Novel Method ◽  
Mutation Assay ◽  
Ethylhexyl Phthalate

Estimation of levels of plasminogen activator (PA)-like protease activity in peripheral blood lymphocytes was demonstrated to be a rapid and sensitive method for screening chemicals with mutagenic activity in mammalian cells. The combination of the PA induction test and K-ras codon 12 mutation assay was suitable for screening the mutagenic chemicals at very low concentrations. Using these methods, the mutagenicity of chlorpropham (CIPC) and di(2-ethylhexyl)phthalate (DEHP) was demonstrated in cultured human cells.

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