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 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 Pathogenetic Substantiation of the Therapeutic Impact on Microbiota in Irritable Bowel Syndrome

2019 ◽  
Vol 29 (4) ◽  
pp. 7-14
Author(s):  
Yu. O. Shulpekova ◽  
G. H. Babaeva ◽  
V. Yu. Rusyaev
Keyword(s):  
Irritable Bowel Syndrome ◽  
Intestinal Microbiota ◽  
Intestinal Bacteria ◽  
Host Cells ◽  
Intestinal Microbiome ◽  
Bacterial Strains ◽  
Blastocystis Hominis ◽  
Therapeutic Impact ◽  
Irritable Bowel ◽  
Positive Effect

Aim. This review aims to describe the nature of changes in the intestinal microbiota in irritable bowel syndrome (IBS) and provide a pathogenetic justification of the feasibility of a therapeutic impact on microbiota. General findings. An important aspect of the interaction of intestinal bacteria with the “host” cells is their contact with pattern recognition receptors of enterocytes, dendritic cell receptors, as well as a transcellular transport of antigens in the region of Peyer’s patches. The area of interaction of intestinal bacteria and the human body is not limited to the intestines. Intestinal bacteria demonstrate a significant humoral effect due to signalling molecules, some of which exhibit neurotransmitter properties. The study of the bacterial cross-feeding for various species, i.e. mutual use of nutrient substrates produced by bacteria of various species, is of a great interest. The development of a lowactivity inflammation in IBS can partly be explained by the increased interaction of flagellin with the corresponding receptor, as well as the influx of excess bacteria from the small intestine. The majority of studies on IBS have demonstrated the predominance of intestinal bacteria with pro-inflammatory potential (Enterobacteriaceae) and the lack of bacteria with a pronounced anti-inflammatory, antimicrobial and enzymatic action (Lactobacillus and Bifidobacterium), as well as increased mucus degradation. Similar changes are observed in inflammatory bowel diseases. Reduced microbial diversity increases susceptibility to intestinal infections and parasitoses, including those caused by protozoa conditionally pathogenic for adults, such as Blastocystis hominis hominis, Dientamoeba fragilis, Giardia lamblia. With the help of nutrition correction, the use of probiotics and functional foods containing certain probiotic strains, plant fibres (primarily psyllium) and, in some cases, nonabsorbable antibiotics, a positive effect can be achieved in a significant number of IBS patients. Recent works have shown that clinical improvement is accompanied by a change in the composition of the intestinal microbiota.Conclusion. For the pathogenetic treatment of irritable bowel syndrome, the use of non-drug treatment is justified, such as diet optimization and prescription of plant fibres and probiotic bacterial strains. The positive effect of such an approach is largely determined by modification of the intestinal microbiota composition. This opens up prospects for a further, more targeted impact on the intestinal microbiome.

scholarly journals Related Enteric Viruses Have Different Requirements for Host Microbiota in Mice

2019 ◽  
Vol 93 (23) ◽  
Author(s):  
Christopher M. Robinson ◽  
Mikal A. Woods Acevedo ◽  
Broc T. McCune ◽  
Julie K. Pfeiffer
Keyword(s):  
Single Dose ◽  
Viral Replication ◽  
Antibiotic Treatment ◽  
Enteric Viruses ◽  
Intestinal Bacteria ◽  
Enteric Virus ◽  
Intestinal Infection ◽  
Bacterial Populations ◽  
Antibiotic Cocktail ◽  
Oral Inoculation

ABSTRACT Accumulating evidence suggests that intestinal bacteria promote enteric virus infection in mice. For example, previous work demonstrated that antibiotic treatment of mice prior to oral infection with poliovirus reduced viral replication and pathogenesis. Here, we examined the effect of antibiotic treatment on infection with coxsackievirus B3 (CVB3), a picornavirus closely related to poliovirus. We treated mice with a mixture of five antibiotics to deplete host microbiota and examined CVB3 replication and pathogenesis following oral inoculation. We found that, as seen with poliovirus, CVB3 shedding and pathogenesis were reduced in antibiotic-treated mice. While treatment with just two antibiotics, vancomycin and ampicillin, was sufficient to reduce CVB3 replication and pathogenesis, this treatment had no effect on poliovirus. The quantity and composition of bacterial communities were altered by treatment with the five-antibiotic cocktail and by treatment with vancomycin and ampicillin. To determine whether more-subtle changes in bacterial populations impact viral replication, we examined viral infection in mice treated with milder antibiotic regimens. Mice treated with one-tenth the standard concentration of the normal antibiotic cocktail supported replication of poliovirus but not CVB3. Importantly, a single dose of one antibiotic, streptomycin, was sufficient to reduce CVB3 shedding and pathogenesis while having no effect on poliovirus shedding and pathogenesis. Overall, replication and pathogenesis of CVB3 are more sensitive to antibiotic treatment than poliovirus, indicating that closely related viruses may differ with respect to their reliance on microbiota. IMPORTANCE Recent data indicate that intestinal bacteria promote intestinal infection of several enteric viruses. Here, we show that coxsackievirus, an enteric virus in the picornavirus family, also relies on microbiota for intestinal replication and pathogenesis. Relatively minor depletion of the microbiota was sufficient to decrease coxsackievirus infection, while poliovirus infection was unaffected. Surprisingly, a single dose of one antibiotic was sufficient to reduce coxsackievirus infection. Therefore, these data indicate that closely related viruses may differ with respect to their reliance on microbiota.

scholarly journals Frequent Coinfection of Cells Explains Functional In Vivo Complementation between Cytomegalovirus Variants in the Multiply Infected Host

2005 ◽  
Vol 79 (15) ◽  
pp. 9492-9502 ◽  
Author(s):  
Luka Čičin-Šain ◽  
Jürgen Podlech ◽  
Martin Messerle ◽  
Matthias J. Reddehase ◽  
Ulrich H. Koszinowski
Keyword(s):  
Fluorescent Protein ◽  
Genetic Recombination ◽  
Viral Fitness ◽  
Host Cells ◽  
Infected Host ◽  
Murine Cytomegalovirus ◽  
Wild Type Virus ◽  
Multiple Infection ◽  
Green Fluorescent Protein Gene ◽  
Multiple Infections

ABSTRACT In contrast to many other virus infections, primary cytomegalovirus (CMV) infection does not fully protect against reinfection. Accordingly, clinical data have revealed a coexistence of multiple human CMV variants/strains in individual patients. Notably, the phenomenon of multiple infection was found to correlate with increased virus load and severity of CMV disease. Although of obvious medical relevance, the mechanism underlying this correlation is unknown. A weak immune response in an individual could be responsible for a more severe disease and for multiple infections. Alternatively, synergistic contributions of variants that differ in their biological properties can lead to qualitative changes in viral fitness by direct interactions such as genetic recombination or functional complementation within coinfected host cells. We have addressed this important question paradigmatically with the murine model by differently designed combinations of two viruses employed for experimental coinfection of mice. Specifically, a murine cytomegalovirus (MCMV) mutant expressing Cre recombinase was combined for coinfection with a mutant carrying Cre-inducible green fluorescent protein gene, and attenuated mutants were combined for coinfection with wild-type virus followed by two-color in situ hybridization studies visualizing the replication of the two viruses in infected host organs. These different approaches concurred in the conclusion that coinfection of host cells is more frequent than statistically predicted and that this coinfection alters virus fitness by functional trans-complementation rather than by genetic recombination. The reported findings make a major contribution to our molecular understanding of enhanced CMV pathogenicity in the multiply infected host.

scholarly journals Development of a Fluorescent In Situ Method for Visualization of Enteric Viruses

2009 ◽  
Vol 75 (24) ◽  
pp. 7822-7827 ◽  
Author(s):  
Helen Rawsthorne ◽  
Trevor G. Phister ◽  
Lee-Ann Jaykus
Keyword(s):  
Mammalian Cells ◽  
Hepatitis A Virus ◽  
Fluorescent Microscopy ◽  
Enteric Viruses ◽  
Fluorescent Labeling ◽  
Host Cells ◽  
Virus Infectivity ◽  
Murine Norovirus ◽  
Sandwich Type

ABSTRACT Studying the interactions between enteric pathogens and their environment is important to improving our understanding of their persistence and transmission. However, this remains challenging in large part because of difficulties associated with tracking pathogens in their natural environment(s). In this study, we report a fluorescent labeling strategy which was applied to murine norovirus (MNV-1), a human norovirus surrogate, and hepatitis A virus (HAV). Specifically, streptavidin-labeled Quantum dots (Q-Dots) were bound to biotinylated capsids of MNV-1 and HAV (bio-MNV-1 and bio-HAV); the process was confirmed by using a sandwich-type approach in which streptavidin-bound plates were reacted with biotinylated virus followed by a secondary binding to Q-Dots with an emission range of 635 to 675 nm (Q-Dots 655). The assay demonstrated a relative fluorescence of 528 ± 48.1 and 112 ± 8.6 for bio-MNV-1 and control MNV-1, respectively. The biotinylation process did not impact virus infectivity, nor did it interfere with the interactions between the virus and host cells or model produce items. Using fluorescent microscopy, it was possible to visualize both bio-HAV and bio-MNV-1 attached to the surfaces of permissive mammalian cells and green onion tissue. The method provides a powerful tool for the labeling and detection of enteric viruses (and their surrogates) which can be used to track virus behavior in situ.

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 Enteric Virus Co-infection of Mammalian Cells and Promote Genetic Recombination

2018 ◽  
Vol 23 (1) ◽  
pp. 77-88.e5 ◽  
Author(s):  
Andrea K. Erickson ◽  
Palmy R. Jesudhasan ◽  
Melinda J. Mayer ◽  
Arjan Narbad ◽  
Sebastian E. Winter ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Genetic Recombination ◽  
Enteric Virus

scholarly journals Related enteric viruses have different requirements for host microbiota in mice

2019 ◽  
Author(s):  
Christopher M. Robinson ◽  
Mikal A. Woods Acevedo ◽  
Broc T. McCune ◽  
Julie K. Pfeiffer
Keyword(s):  
Single Dose ◽  
Virus Infection ◽  
Viral Replication ◽  
Antibiotic Treatment ◽  
Enteric Viruses ◽  
Intestinal Bacteria ◽  
Enteric Virus ◽  
Bacterial Populations ◽  
Antibiotic Cocktail ◽  
Oral Inoculation

AbstractAccumulating evidence suggests that intestinal bacteria promote enteric virus infection in mice. For example, previous work demonstrated that antibiotic treatment of mice prior to oral infection with poliovirus reduced viral replication and pathogenesis. Here we examined the effect of antibiotic treatment on infection with coxsackievirus B3 (CVB3), a picornavirus closely related to poliovirus. We treated mice with a mixture of five antibiotics to deplete host microbiota and examined CVB3 replication and pathogenesis following oral inoculation. We found that, like poliovirus, CVB3 shedding and pathogenesis were reduced in antibiotic-treated mice. While treatment with just two antibiotics, vancomycin and ampicillin, was sufficient to reduce CVB3 replication and pathogenesis, this treatment had no effect on poliovirus. Quantity and composition of bacterial communities were altered by treatment with the five antibiotic cocktail and by treatment with vancomycin and ampicillin. To determine whether more subtle changes in bacterial populations impact viral replication, we examined viral infection in mice treated with milder antibiotic regimens. Mice treated with one-tenth the concentration of the normal antibiotic cocktail supported replication of poliovirus but not CVB3. Importantly, a single dose of one antibiotic, streptomycin, was sufficient to reduce CVB3 shedding and pathogenesis, while having no effect on poliovirus shedding and pathogenesis. Overall, replication and pathogenesis of CVB3 is more sensitive to antibiotic treatment than poliovirus, indicating that closely related viruses may differ in their reliance on microbiota.ImportanceRecent data indicate that intestinal bacteria promote intestinal infection of several enteric viruses. Here we show that coxsackievirus, an enteric virus in the picornavirus family, also relies on microbiota for intestinal replication and pathogenesis. Relatively minor depletion of the microbiota was sufficient to decrease coxsackievirus infection, while poliovirus infection was unaffected. Surprisingly, a single dose of one antibiotic was sufficient to reduce coxsackievirus infection. Therefore, these data indicate that microbiota can influence enteric virus infection through distinct mechanisms, even for closely related viruses.

scholarly journals On the origin and evolution of SARS-CoV-2

2021 ◽  
Author(s):  
Devika Singh ◽  
Soojin V. Yi
Keyword(s):  
Mammalian Cells ◽  
Genetic Recombination ◽  
Disease Outbreaks ◽  
Purifying Selection ◽  
Host Cells ◽  
Human Populations ◽  
S Protein ◽  
Origin And Evolution ◽  
Multiple Species ◽  
The Impact

AbstractThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing global outbreak of a coronavirus disease (herein referred to as COVID-19). Other viruses in the same phylogenetic group have been responsible for previous regional outbreaks, including SARS and MERS. SARS-CoV-2 has a zoonotic origin, similar to the causative viruses of these previous outbreaks. The repetitive introduction of animal viruses into human populations resulting in disease outbreaks suggests that similar future epidemics are inevitable. Therefore, understanding the molecular origin and ongoing evolution of SARS-CoV-2 will provide critical insights for preparing for and preventing future outbreaks. A key feature of SARS-CoV-2 is its propensity for genetic recombination across host species boundaries. Consequently, the genome of SARS-CoV-2 harbors signatures of multiple recombination events, likely encompassing multiple species and broad geographic regions. Other regions of the SARS-CoV-2 genome show the impact of purifying selection. The spike (S) protein of SARS-CoV-2, which enables the virus to enter host cells, exhibits signatures of both purifying selection and ancestral recombination events, leading to an effective S protein capable of infecting human and many other mammalian cells. The global spread and explosive growth of the SARS-CoV-2 population (within human hosts) has contributed additional mutational variability into this genome, increasing opportunities for future recombination.

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