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 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 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 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 Review of the Genotoxicity of Triallate

2003 ◽  
Vol 22 (3) ◽  
pp. 233-251 ◽  
Author(s):  
Charles E. Healy ◽  
Larry D. Kier ◽  
Fabrice Broeckaert ◽  
Mark A. Martens
Keyword(s):  
Dna Synthesis ◽  
Mammalian Cells ◽  
Mutagenic Activity ◽  
Human Lymphocytes ◽  
In Vivo Studies ◽  
Weight Of Evidence ◽  
Unscheduled Dna Synthesis ◽  
Vitro Assay

Triallate is a selective herbicidal chemical used for control of wild oats in wheat. It has an extensive genotoxicity database that includes a variety of in vitro and in vivo studies. The chemical has produced mixed results in in vitro assay systems. It was genotoxic in bacterial mutation Ames assays, predominantly in Salmonella typhimurium strains TA100 and TA1535 in the presence of S9. Weaker responses have been observed in TA100 and TA1535 in the absence of S9. Mixed results have been observed in strain TA98, whereas no genotoxicity has been observed in strains TA1537 and TA1538. The presence and absence of S9 and its source seem to play a role in the bacterial response to the chemical. There have also been conflicting results in other test systems using other bacterial genera, yeast, and mammalian cells. Chromosome effects assays (sister-chromatid exchange and cytogenetics assays) have produced mixed results with S9 but no genotoxicity without S9. Triallate has not produced any genotoxicity in in vitro DNA damage or unscheduled DNA synthesis assays using EUE cells, human lymphocytes, and rat and mouse hepatocytes. In a series of in vivo genotoxicity assays (cytogenetics, micronucleus, dominant lethal, and unscheduled DNA synthesis), there has been no indication of any adverse genotoxic effect. Metabolism data indicate that the probable explanation for the differences observed between the in vitro studies with S9 and without S9 and between the in vitro and the in vivo studies is the production of a mutagenic intermediate in vitro at high doses of triallate is expected to be at most only transiently present in in vivo studies. The weight of evidence strongly suggests that triallate is not likely to exert mutagenic activity in vivo due to toxicokinetics and metabolic processes leading to detoxification.

scholarly journals Incomplete influenza A virus genomes are abundant but readily complemented during spatially structured viral spread

2019 ◽  
Author(s):  
Nathan T. Jacobs ◽  
Nina O. Onuoha ◽  
Alice Antia ◽  
Rustom Antia ◽  
John Steel ◽  
...  
Keyword(s):  
Influenza A ◽  
Mutant Virus ◽  
Viral Fitness ◽  
H3n2 Virus ◽  
Multiple Infection ◽  
Mixed System ◽  
Viral Genomes ◽  
Viral Spread ◽  
A Cell

AbstractViral genomes comprising multiple distinct RNA segments can undergo genetic exchange through reassortment, a process that facilitates viral evolution and can have major epidemiological consequences. Segmentation also allows the replication of incomplete viral genomes (IVGs), however, and evidence suggests that IVGs occur frequently for influenza A viruses. Here we quantified the frequency of IVGs using a novel single cell assay and then examined their implications for viral fitness. We found that each segment of influenza A/Panama/2007/99 (H3N2) virus has only a 58% probability of being present in a cell infected with a single virion. These observed frequencies accurately account for the abundant reassortment seen in co-infection, and suggest that an average of 3.7 particles are required for replication of a full viral genome in a cell. This dependence on multiple infection is predicted to decrease infectivity and to slow viral propagation in a well-mixed system. Importantly, however, modeling of spatially structured viral growth predicted that the need for complementation is met more readily when secondary spread occurs locally. This expectation was supported by experimental infections in which the level spatial structure was manipulated. Furthermore, a virus engineered to be entirely dependent on co-infection to replicate in vivo was found to grow robustly in guinea pigs, suggesting that coinfection is sufficiently common in vivo to support propagation of IVGs. The infectivity of this mutant virus was, however, reduced 815-fold relative wild-type and the mutant virus did not transmit to contacts. Thus, while incomplete genomes augment reassortment and contribute to within-host spread, the existence of rare complete IAV genomes may be critical for transmission to new hosts.

Vacuoles Induced in Mammalian Cells by Helicobacter Cytotoxin are Acidic Organelles

1990 ◽  
Vol 48 (3) ◽  
pp. 168-169
Author(s):  
M. H. Chestnut ◽  
C. E. Catrenich
Keyword(s):  
Acridine Orange ◽  
Mammalian Cells ◽  
Laser Scanning ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Ulcer Disease ◽  
Gastroduodenal Disease ◽  
H Pylori

Helicobacter pylori is a non-invasive, Gram-negative spiral bacterium first identified in 1983, and subsequently implicated in the pathogenesis of gastroduodenal disease including gastritis and peptic ulcer disease. Cytotoxic activity, manifested by intracytoplasmic vacuolation of mammalian cells in vitro, was identified in 55% of H. pylori strains examined. The vacuoles increase in number and size during extended incubation, resulting in vacuolar and cellular degeneration after 24 h to 48 h. Vacuolation of gastric epithelial cells is also observed in vivo during infection by H. pylori. A high molecular weight, heat labile protein is believed to be responsible for vacuolation and to significantly contribute to the development of gastroduodenal disease in humans. The mechanism by which the cytotoxin exerts its effect is unknown, as is the intracellular origin of the vacuolar membrane and contents. Acridine orange is a membrane-permeant weak base that initially accumulates in low-pH compartments. We have used acridine orange accumulation in conjunction with confocal laser scanning microscopy of toxin-treated cells to begin probing the nature and origin of these vacuoles.

Cytological changes induced by platinum-thymine in sarcoma-180 cells: Electron microscopy study

1990 ◽  
Vol 48 (3) ◽  
pp. 290-291
Author(s):  
Gustav Ofosu
Keyword(s):  
Mammalian Cells ◽  
Antitumor Agent ◽  
Microscopy Study ◽  
Electron Microscopy Study ◽  
Limiting Factor ◽  
Sarcoma 180 ◽  
Electron Microscopic ◽  
Cytological Changes

Platinum-thymine has been found to be a potent antitumor agent, which is quite soluble in water, and lack nephrotoxicity as the dose-limiting factor. The drug has been shown to interact with DNA and inhibits DNA, RNA and protein synthesis in mammalian cells in vitro. This investigation was undertaken to elucidate the cytotoxic effects of piatinum-thymine on sarcoma-180 cells in vitro ultrastructurally, Sarcoma-180 tumor bearing mice were treated with intraperitoneal injection of platinum-thymine 40mg/kg. A concentration of 60μg/ml dose of platinum-thymine was used in in vitro experiments. Treatments were at varying time intervals of 3, 7 and 21 days for in vivo experiments, and 30, 60 and 120 min., 6, 12, and 24th in vitro. Controls were not treated with platinum-thymine.Electron microscopic analyses of the treated cells in vivo and in vitro showed drastic cytotoxic effect.

DEGRADATION OF MESSENGER RNA IN MAMMALIAN CELLS

1972 ◽  
Vol 71 (2_Suppla) ◽  
pp. S369-S380 ◽  
Author(s):  
Francis T. Kenney ◽  
Kai-Lin Lee ◽  
Charles D. Stiles
Keyword(s):  
Messenger Rna ◽  
Mammalian Cells ◽  
Messenger Rnas ◽  
Tyrosine Transaminase

ABSTRACT Analyses of the response of hydrocortisone-induced tyrosine transaminase in cultured H-35 cells to inhibitors of translation (cycloheximide, puromycin) suggest: (1) that bound ribosomes stabilize messenger RNA in vivo; (2) that messenger is degraded at a rate determined by the rate of translation. Since specific messenger RNAs of mammalian cells are degraded at quite different rates, there may be extensive heterogeneity either in the rate at which ribosomes traverse different messengers or in the number of ribosomes which translate specific messenger RNAs.

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