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PLoS Computational Biology Nov 2022The concept of a nucleic acid barcode applied to pathogen genomes is easy to grasp and the many possible uses are straightforward. But implementation may not be easy,...
The concept of a nucleic acid barcode applied to pathogen genomes is easy to grasp and the many possible uses are straightforward. But implementation may not be easy, especially when growing through multiple generations or assaying the pathogen long-term. The potential problems include: the barcode might alter fitness, the barcode may accumulate mutations, and construction of the marked pathogens may result in unintended barcodes that are not as designed. Here, we generate approximately 5,000 randomized barcodes in the genome of the prototypic small DNA virus murine polyomavirus. We describe the challenges faced with interpreting the barcode sequences obtained from the library. Our Illumina NextSeq sequencing recalled much greater variation in barcode sequencing reads than the expected 5,000 barcodes-necessarily stemming from the Illumina library processing and sequencing error. Using data from defined control virus genomes cloned into plasmid backbones we develop a vetted post-sequencing method to cluster the erroneous reads around the true virus genome barcodes. These findings may foreshadow problems with randomized barcodes in other microbial systems and provide a useful approach for future work utilizing nucleic acid barcoded pathogens.
Topics: Mice; Animals; DNA Viruses; Nucleic Acids
PubMed: 36413582
DOI: 10.1371/journal.pcbi.1010131 -
Biochimie Nov 2015Hypersaline waters and salt crystals are known to contain high numbers of haloarchaeal cells and their viruses. Both culture-dependent and culture-independent studies...
Hypersaline waters and salt crystals are known to contain high numbers of haloarchaeal cells and their viruses. Both culture-dependent and culture-independent studies indicate that these viruses represent a world-wide distributed reservoir of orphan genes and possibly novel virion morphotypes. To date, 90 viruses have been described for halophilic archaeal hosts, all belonging to the Halobacteriaceae family. This number is higher than that described for the members of any other archaeal family, but still very low compared to the viruses of bacteria and eukaryotes. The known haloarchaeal viruses represent icosahedral tailed, icosahedral internal membrane-containing, pleomorphic, and spindle-shaped virion morphotypes. This morphotype distribution is low, especially when compared to the astronomical number (>10(31)) of viruses on Earth. This strongly suggests that only certain protein folds are capable of making a functional virion. Viruses infecting cells belonging to any of the three domains of life are known to share similar major capsid protein folds which can be used to classify viruses into structure-based lineages. The latest observation supporting this proposal comes from the studies of icosahedral tailed haloarchaeal viruses which are the most abundant virus isolates from hypersaline environments. These viruses were shown to have the same major capsid protein fold (HK97-fold) with tailed bacteriophages belonging to the order Caudovirales and with eukaryotic herpes viruses. This proposes that these viruses have a common origin dating back to ancient times. Here we summarize the current knowledge of haloarchaeal viruses from the perspective of virus morphotypes.
Topics: DNA Viruses; Halobacteriaceae; Microscopy, Electron, Transmission
PubMed: 26151345
DOI: 10.1016/j.biochi.2015.07.002 -
Virus Research Apr 2017
Topics: DNA Viruses; DNA-Directed DNA Polymerase; DNA-Directed RNA Polymerases; Humans; RNA Viruses; Virus Replication
PubMed: 28188807
DOI: 10.1016/j.virusres.2017.02.003 -
Microbiology and Molecular Biology... Sep 2017The past 17 years have been marked by a revolution in our understanding of cellular multisubunit DNA-dependent RNA polymerases (MSDDRPs) at the structural level. A... (Review)
Review
The past 17 years have been marked by a revolution in our understanding of cellular multisubunit DNA-dependent RNA polymerases (MSDDRPs) at the structural level. A parallel development over the past 15 years has been the emerging story of the giant viruses, which encode MSDDRPs. Here we link the two in an attempt to understand the specialization of multisubunit RNA polymerases in the domain of life encompassing the large nucleocytoplasmic DNA viruses (NCLDV), a superclade that includes the giant viruses and the biochemically well-characterized poxvirus vaccinia virus. The first half of this review surveys the recently determined structural biology of cellular RNA polymerases for a microbiology readership. The second half discusses a reannotation of MSDDRP subunits from NCLDV families and the apparent specialization of these enzymes by virus family and by subunit with regard to subunit or domain loss, subunit dissociability, endogenous control of polymerase arrest, and the elimination/customization of regulatory interactions that would confer higher-order cellular control. Some themes are apparent in linking subunit function to structure in the viral world: as with cellular RNA polymerases I and III and unlike cellular RNA polymerase II, the viral enzymes seem to opt for speed and processivity and seem to have eliminated domains associated with higher-order regulation. The adoption/loss of viral RNA polymerase proofreading functions may have played a part in matching intrinsic mutability to genome size.
Topics: Cytoplasm; DNA Viruses; DNA-Directed RNA Polymerases; Evolution, Molecular; Genes, Viral; Phylogeny; Transcription, Genetic; Vaccinia virus; Viral Proteins
PubMed: 28701329
DOI: 10.1128/MMBR.00010-17 -
Journal of Clinical Virology : the... Oct 2020Redondovirus (ReDoV) is a recently discovered circular, Rep-encoding single-stranded DNA (CRESS-DNA) virus in humans. Its pathogenesis and clinical associations are...
BACKGROUND
Redondovirus (ReDoV) is a recently discovered circular, Rep-encoding single-stranded DNA (CRESS-DNA) virus in humans. Its pathogenesis and clinical associations are still completely unknown.
METHODS
The presence of ReDoV DNA was investigated in biological specimens of 543 Italian subjects by in-house developed PCR assays.
RESULTS
The overall ReDoV prevalence was about 4% (23 of 543 samples). The virus was detected in 22 of 209 (11 %) respiratory samples. One stool sample was also ReDoV positive. Viral DNA was not found in blood samples from immunocompetent and immunosuppressed subjects and cerebrospinal fluids from patients with neurological diseases. Genomic nucleotide differences were detected among the ReDoV isolates by sequencing a 582-nucleotide fragment of the capsid gene of the viral genome.
CONCLUSIONS
The results demonstrate that ReDoV is mainly present in the respiratory tract of infected people. Further investigations are needed to reveal possible clinical implications of this new CRESS-DNA virus in humans.
Topics: Adult; Aged; Capsid Proteins; DNA Virus Infections; DNA Viruses; DNA, Viral; Feces; Female; Genetic Variation; Genome, Viral; Humans; Italy; Male; Middle Aged; Phylogeny; Prevalence; Respiratory Tract Infections; Retrospective Studies; Sequence Analysis, DNA
PubMed: 32841923
DOI: 10.1016/j.jcv.2020.104586 -
Philosophical Transactions of the Royal... May 2019One out of 10 cancers is estimated to arise from infections by a handful of oncogenic viruses. These infectious cancers constitute an opportunity for primary prevention...
One out of 10 cancers is estimated to arise from infections by a handful of oncogenic viruses. These infectious cancers constitute an opportunity for primary prevention through immunization against the viral infection, for early screening through molecular detection of the infectious agent, and potentially for specific treatments, by targeting the virus as a marker of cancer cells. Accomplishing these objectives will require a detailed understanding of the natural history of infections, the mechanisms by which the viruses contribute to disease, the mutual adaptation of viruses and hosts, and the possible viral evolution in the absence and in the presence of the public health interventions conceived to target them. This issue showcases the current developments in experimental tissue-like and animal systems, mathematical models and evolutionary approaches to understand DNA oncoviruses. Our global aim is to provide proximate explanations to the present-day interface and interactions between virus and host, as well as ultimate explanations about the adaptive value of these interactions and about the evolutionary pathways that have led to the current malignant phenotype of oncoviral infections. This article is part of the theme issue 'Silent cancer agents: multi-disciplinary modelling of human DNA oncoviruses'.
Topics: Animals; DNA Virus Infections; DNA Viruses; Evolution, Molecular; Humans; Oncogenic Viruses; Tumor Virus Infections; Virulence
PubMed: 30955496
DOI: 10.1098/rstb.2019.0041 -
International Journal of Molecular... Jul 2018Since being first described more than 60 years ago, Na,K-ATPase has been extensively studied, while novel concepts about its structure, physiology, and biological roles... (Review)
Review
Since being first described more than 60 years ago, Na,K-ATPase has been extensively studied, while novel concepts about its structure, physiology, and biological roles continue to be elucidated. Cardiac glycosides not only inhibit the pump function of Na,K-ATPase but also activate intracellular signal transduction pathways, which are important in many biological processes. Recently, antiviral effects have been described as a novel feature of Na,K-ATPase inhibition with the use of cardiac glycosides. Cardiac glycosides have been reported to be effective against both DNA viruses such as cytomegalovirus and herpes simplex and RNA viruses such as influenza, chikungunya, coronavirus, and respiratory syncytial virus, among others. Consequently, cardiac glycosides have emerged as potential broad-spectrum antiviral drugs, with the great advantage of targeting cell host proteins, which help to minimize resistance to antiviral treatments, making them a very promising strategy against human viral infections. Here, we review the effect of cardiac glycosides on viral biology and the mechanisms by which these drugs impair the replication of this array of different viruses.
Topics: Antiviral Agents; Cardiac Glycosides; DNA Virus Infections; DNA Viruses; Enzyme Inhibitors; Humans; RNA Virus Infections; RNA Viruses; Signal Transduction; Sodium-Potassium-Exchanging ATPase
PubMed: 30042322
DOI: 10.3390/ijms19082154 -
Microbiome Jan 2021Polintons are large mobile genetic elements found in the genomes of eukaryotic organisms that are considered the ancient ancestors of most eukaryotic dsDNA viruses....
BACKGROUND
Polintons are large mobile genetic elements found in the genomes of eukaryotic organisms that are considered the ancient ancestors of most eukaryotic dsDNA viruses. Originally considered as transposons, they have been found to encode virus capsid genes, suggesting they may actually be integrated viruses; however, an extracellular form has yet to be detected. Recently, circa 25 Polinton-like viruses have been discovered in environmental metagenomes and algal genomes, which shared distantly related genes to both Polintons and virophages (Lavidaviridae). These entities could be the first members of a major class of ancient eukaryotic viruses; however, owing to the lack of available genomes for analysis, information on their global diversity, evolutionary relationships, eukaryotic hosts, and status as free virus particles is limited.
RESULTS
Here, we analysed the metaviromes of an alpine lake to show that Polinton-like virus genome sequences are abundant in the water column. We identify major capsid protein genes belonging to 82 new Polinton-like viruses and use these to interrogate publicly available metagenomic datasets, identifying 543 genomes and a further 16 integrated into eukaryotic genomes. Using an analysis of shared gene content and major capsid protein phylogeny, we define large groups of Polinton-like viruses and link them to diverse eukaryotic hosts, including a new group of viruses, which possess all the core genes of virophages and infect oomycetes and Chrysophyceae.
CONCLUSIONS
Our study increased the number of known Polinton-like viruses by 25-fold, identifying five major new groups of eukaryotic viruses, which until now have been hidden in metagenomic datasets. The large enrichment (> 100-fold) of Polinton-like virus sequences in the virus-sized fraction of this alpine lake and the fact that their viral major capsid proteins are found in eukaryotic host transcriptomes support the hypothesis that Polintons in unicellular eukaryotes are viruses. In summary, our data reveals a diverse assemblage of globally distributed viruses, associated with a wide range of unicellular eukaryotic hosts. We anticipate that the methods we have developed for Polinton-like virus detection and the database of over 20,000 genes we present will allow for continued discovery and analysis of these new viral groups. Video abstract.
Topics: Aquatic Organisms; DNA Viruses; DNA, Viral; Ecosystem; Eukaryota; Genome, Viral; Lakes; Phylogeny; Virophages; Virus Integration
PubMed: 33436089
DOI: 10.1186/s40168-020-00956-0 -
Viruses Jan 2020DNA viruses that replicate in the nucleus encompass a range of ubiquitous and clinically important viruses, from acute pathogens to persistent tumor viruses. These... (Review)
Review
DNA viruses that replicate in the nucleus encompass a range of ubiquitous and clinically important viruses, from acute pathogens to persistent tumor viruses. These viruses must co-opt nuclear processes for the benefit of the virus, whilst evading host processes that would otherwise attenuate viral replication. Accordingly, DNA viruses induce the formation of membraneless assemblies termed viral replication compartments (VRCs). These compartments facilitate the spatial organization of viral processes and regulate virus-host interactions. Here, we review advances in our understanding of VRCs. We cover their initiation and formation, their function as the sites of viral processes, and aspects of their composition and organization. In doing so, we highlight ongoing and emerging areas of research highly pertinent to our understanding of nuclear-replicating DNA viruses.
Topics: Cell Nucleus; DNA Viruses; Host Microbial Interactions; Humans; Viral Proteins; Viral Replication Compartments; Virus Replication
PubMed: 32013091
DOI: 10.3390/v12020151 -
Journal of Invertebrate Pathology Jul 2017In this review we provide an overview of the diversity of large DNA viruses known to be pathogenic for invertebrates. We present their taxonomical classification and... (Review)
Review
In this review we provide an overview of the diversity of large DNA viruses known to be pathogenic for invertebrates. We present their taxonomical classification and describe the evolutionary relationships among various groups of invertebrate-infecting viruses. We also indicate the relationships of the invertebrate viruses to viruses infecting mammals or other vertebrates. The shared characteristics of the viruses within the various families are described, including the structure of the virus particle, genome properties, and gene expression strategies. Finally, we explain the transmission and mode of infection of the most important viruses in these families and indicate, which orders of invertebrates are susceptible to these pathogens.
Topics: Animals; DNA Virus Infections; DNA Viruses; Disease Susceptibility; Genetic Variation; Genome, Viral; Invertebrates
PubMed: 27592378
DOI: 10.1016/j.jip.2016.08.001