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The Journal of General Virology Nov 2021Viral metagenomic studies have enabled the discovery of many unknown viruses and revealed that viral communities are much more diverse and ubiquitous than previously...
Viral metagenomic studies have enabled the discovery of many unknown viruses and revealed that viral communities are much more diverse and ubiquitous than previously thought. Some viruses have multiple genome components that are encapsidated either in separate virions (multipartite viruses) or in the same virion (segmented viruses). In this study, we identify what is possibly a novel bipartite plant-associated circular single-stranded DNA virus in a wild prickly pear cactus, , that is endemic to the Chaco ecoregion in South America. Two ~1.8 kb virus-like circular DNA components were recovered, one encoding a replication-associated protein (Rep) and the other a capsid protein (CP). Both of the inferred protein sequences of the Rep and CP are homologous to those encoded by members of the family . These two putatively cognate components each have a nonanucleotide sequence within a likely hairpin structure that is homologous to the origins of rolling-circle replication (RCR), found in diverse circular single-stranded DNA viruses. In addition, the two components share similar putative replication-associated iterative sequences (iterons), which in circular single-stranded DNA viruses are important for Rep binding during the initiation of RCR. Such molecular features provide support for the possible bipartite nature of this virus, which we named utkilio virus (common name of the in South America) components A and B. In the infectivity assays conducted in plants, only the A component of utkilio virus, which encodes the Rep protein, was found to move and replicate systemically in . This was not true for component B, for which we did not detect replication, which may have been due to this being a defective molecule or because of the model plants () used for the infection assays. Future experiments need to be conducted with other plants, including , to understand more about the biology of these viral components.
Topics: Amino Acid Sequence; Base Sequence; DNA Viruses; DNA, Circular; DNA, Viral; Geminiviridae; Genome, Viral; Opuntia; Phylogeny; Plant Diseases; Viral Proteins
PubMed: 34726588
DOI: 10.1099/jgv.0.001671 -
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 -
Virus Research Jun 2023Virome exploration from the freshwater stream ecosystem is less explored. We deciphered the DNA virome from sediments of the N-Choe stream in Chandigarh, India. This...
Virome exploration from the freshwater stream ecosystem is less explored. We deciphered the DNA virome from sediments of the N-Choe stream in Chandigarh, India. This study utilized the long-read nanopore sequencing data analyzed by assembly-free and assembly-based approaches to study the viral community structure and its genetic potential. In the classified fraction of the virome, we observed the dominance of the ssDNA viruses. The prominent ssDNA virus families were Microviridae, Circoviridae, and Genomoviridae. The majority of dsDNA viruses were bacteriophages belonging to class Caudoviricetes. We also recovered metagenome-assembled viruses of Microviridae, CRESS DNA viruses, and viral-like circular molecules. We identified the structural and functional gene repertoire of the viromes and their gene ontology. Furthermore, we detected auxiliary metabolic genes (AMGs) involved in pathways such as pyrimidine synthesis, organosulfur metabolism indicating the functional importance of viruses in the ecosystem. The antibiotic resistance genes (ARGs), metal resistance genes (MRGs), and mobile genetic elements (MGEs) present in the viromes and their co-occurrence were studied. ARGs of the glycopeptide, macrolide, lincosamide, streptogramin (MLS), and mupirocin categories were well represented. Among the reads containing ARGs, a few reads were also classified as viruses, indicating that environmental viruses act as reservoirs of ARGs.
Topics: Rivers; Ecosystem; DNA Viruses; Viruses; Bacteriophages; Metagenomics
PubMed: 37031921
DOI: 10.1016/j.virusres.2023.199110 -
Biochemical and Biophysical Research... May 2020Upon detection of viral DNA, the cytoplasmic DNA sensor cyclic GMP-AMP (cGAMP) synthase (cGAS) utilizes GTP and ATP as substrates to synthesize the second messenger...
Upon detection of viral DNA, the cytoplasmic DNA sensor cyclic GMP-AMP (cGAMP) synthase (cGAS) utilizes GTP and ATP as substrates to synthesize the second messenger molecule 2'3'cyclic GMP-AMP (cGAMP), which binds to the ER-associated adaptor protein MITA/STING to signal innate antiviral response to DNA virus. How the cGAS-MITA pathways are post-translationally regulated is not fully understood. In this study, we identified the tyrosine kinase CSK as a positive regulator of cGAS-MITA mediated innate antiviral response. CSK-deficiency inhibits DNA virus-triggered induction of downstream antiviral effector genes. Following DNA virus infection, CSK phosphorylates MITA at Y240 and Y245, which is important for its activation. These results suggest that CSK plays a role in modulating innate immune response to DNA virus.
Topics: Animals; CSK Tyrosine-Protein Kinase; Cell Line; DNA Viruses; Humans; Immunity, Innate; Membrane Proteins; Mice, Inbred C57BL; Mice, Knockout; Phosphorylation
PubMed: 32201077
DOI: 10.1016/j.bbrc.2020.03.069 -
Scientific Reports Mar 2021Bioconversion of organic materials is the foundation of many applications in chemical engineering, microbiology and biochemistry. Herein, we introduce a new methodology...
Bioconversion of organic materials is the foundation of many applications in chemical engineering, microbiology and biochemistry. Herein, we introduce a new methodology to quantitatively determine conversion of biomass in viral infections while simultaneously imaging morphological changes of the host cell. As proof of concept, the viral replication of an unidentified giant DNA virus and the cellular response of an amoebal host are studied using soft X-ray microscopy, titration dilution measurements and thermal gravimetric analysis. We find that virions produced inside the cell are visible from 18 h post infection and their numbers increase gradually to a burst size of 280-660 virions. Due to the large size of the virion and its strong X-ray absorption contrast, we estimate that the burst size corresponds to a conversion of 6-12% of carbonaceous biomass from amoebal host to virus. The occurrence of virion production correlates with the appearance of a possible viral factory and morphological changes in the phagosomes and contractile vacuole complex of the amoeba, whereas the nucleus and nucleolus appear unaffected throughout most of the replication cycle.
Topics: Acanthamoeba; Biomass; DNA Viruses; DNA, Viral; Genome, Viral; Giant Viruses; Host-Pathogen Interactions; Phagosomes; Soil Microbiology; Thermogravimetry; Vacuoles; Virion; Virus Replication; X-Ray Microtomography
PubMed: 33658544
DOI: 10.1038/s41598-021-83547-9 -
Oncogene Aug 2006RB, the most investigated tumor suppressor gene, is the founder of the RB family of growth/tumor suppressors, which comprises also p107 (RBL1) and Rb2/p130 (RBL2). The... (Review)
Review
RB, the most investigated tumor suppressor gene, is the founder of the RB family of growth/tumor suppressors, which comprises also p107 (RBL1) and Rb2/p130 (RBL2). The protein products of these genes, pRb, p107 and pRb2/p130, respectively, are also known as 'pocket proteins', because they share a 'pocket' domain responsible for most of the functional interactions characterizing the activity of this family of cellular factors. The interest in these genes and proteins springs essentially from their ability to regulate negatively cell cycle processes and for their ability to slow down or abrogate neoplastic growth. The pocket domain of the RB family proteins is dramatically hampered in its functions by the interference of a number of proteins produced by the small DNA viruses. In the last two decades, the 'viral hypothesis' of cancer has received a considerable renewed impulse from the notion that small DNA viruses, such as Adenovirus, Human papillomavirus (HPV) and Polyomavirus, produce factors that can physically interact with major cellular regulators and alter their function. These viral proteins (oncoproteins) act as multifaceted molecular devices that have evolved to perform very specific tasks. Owing to these features, viral oncoproteins have been widely employed as invaluable experimental tools for the identification of several key families of regulators, particularly of the cell cycle homeostasis. Adenovirus early-region 1A (E1A) is the most widely investigated small DNA tumor virus oncoprotein, but relevant interest in human oncology is raised by the E1A-related E7 protein from transforming HPV strains and by Polyomavirus oncoproteins, particularly large and small T antigens from Simian virus 40, JC virus and BK virus.
Topics: Adenoviridae; Animals; Antigens, Polyomavirus Transforming; DNA Viruses; Humans; Oncogene Proteins; Papillomaviridae; Retinoblastoma Protein
PubMed: 16936748
DOI: 10.1038/sj.onc.1209621 -
Virology Journal Apr 2020Musk deer can produce musk which has high medicinal value and is closely related to human health. Viruses in forest musk deer both threaten the health of forest musk...
BACKGROUND
Musk deer can produce musk which has high medicinal value and is closely related to human health. Viruses in forest musk deer both threaten the health of forest musk deer and human beings.
METHODS
Using viral metagenomics we investigated the virome in 85 faeces samples collected from forest musk deer.
RESULTS
In this article, eight novel CRESS-DNA viruses were characterized, whole genomes were 2148 nt-3852 nt in length. Phylogenetic analysis indicated that some viral genomes were part of four different groups of CRESS-DNA virus belonging in the unclassified CRESS-DNA virus, Smacoviridae, pCPa-like virus and pPAPh2-like virus. UJSL001 (MN621482), UJSL003 (MN621469) and UJSL017 (MN621476) fall into the branch of unclassified CRESS-DNA virus (CRESSV1-2), UJSL002 (MN621468), UJSL004 (MN621481) and UJSL007 (MN621470) belong to the cluster of Smacoviridae, UJSL005 (MN604398) showing close relationship with pCPa-like (pCRESS4-8) clusters and UJSL006 (MN621480) clustered into the branch of pPAPh2-like (pCRESS9) virus, respectively.
CONCLUSION
The virome in faeces samples of forest musk deer from Chengdu, Sichuan province, China was revealed, which further characterized the diversity of viruses in forest musk deer intestinal tract.
Topics: Animals; China; DNA Viruses; DNA, Viral; Deer; Feces; Metagenomics; Phylogeny; Virome
PubMed: 32334626
DOI: 10.1186/s12985-020-01332-y -
Virus Research Jan 2021RNA helicase A (RHA) is a ubiquitously expressed DExH-box helicase enzyme that is involved in a wide range of biological processes including transcription, translation,... (Review)
Review
RNA helicase A (RHA) is a ubiquitously expressed DExH-box helicase enzyme that is involved in a wide range of biological processes including transcription, translation, and RNA processing. A number of RNA viruses recruit RHA to the viral RNA to facilitate virus replication. DNA viruses contain a DNA genome and replicate using a DNA-dependent DNA polymerase. RHA has also been reported to associate with some DNA viruses during replication, in which the enzyme acts on the viral RNA or protein products. As shown for Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus, RHA has potential to allow the virus to control a switch in cellular gene expression to modulate the antiviral response. While the study of the interaction of RHA with DNA viruses is still at an early stage, preliminary evidence indicates that the underlying molecular mechanisms are diverse. We now review the current status of this emerging field.
Topics: DEAD-box RNA Helicases; DNA Replication; DNA Viruses; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Herpesvirus 8, Human; Host Microbial Interactions; Humans; Neoplasm Proteins; RNA, Viral; Virus Replication
PubMed: 33132162
DOI: 10.1016/j.virusres.2020.198206 -
Microbiology and Molecular Biology... Jun 2018When a virus infects a host cell, it hijacks the biosynthetic capacity of the cell to produce virus progeny, a process that may take less than an hour or more than a... (Review)
Review
When a virus infects a host cell, it hijacks the biosynthetic capacity of the cell to produce virus progeny, a process that may take less than an hour or more than a week. The overall time required for a virus to reproduce depends collectively on the rates of multiple steps in the infection process, including initial binding of the virus particle to the surface of the cell, virus internalization and release of the viral genome within the cell, decoding of the genome to make viral proteins, replication of the genome, assembly of progeny virus particles, and release of these particles into the extracellular environment. For a large number of virus types, much has been learned about the molecular mechanisms and rates of the various steps. However, in only relatively few cases during the last 50 years has an attempt been made-using mathematical modeling-to account for how the different steps contribute to the overall timing and productivity of the infection cycle in a cell. Here we review the initial case studies, which include studies of the one-step growth behavior of viruses that infect bacteria (Qβ, T7, and M13), human immunodeficiency virus, influenza A virus, poliovirus, vesicular stomatitis virus, baculovirus, hepatitis B and C viruses, and herpes simplex virus. Further, we consider how such models enable one to explore how cellular resources are utilized and how antiviral strategies might be designed to resist escape. Finally, we highlight challenges and opportunities at the frontiers of cell-level modeling of virus infections.
Topics: Animals; DNA Viruses; Genome, Viral; Host-Pathogen Interactions; Humans; Kinetics; Models, Theoretical; RNA Viruses; Viral Proteins; Virus Diseases; Virus Replication
PubMed: 29592895
DOI: 10.1128/MMBR.00066-17 -
Annual Review of Virology Sep 2017Circular single-stranded DNA viruses infect archaea, bacteria, and eukaryotic organisms. The relatively recent emergence of single-stranded DNA viruses, such as chicken... (Review)
Review
Circular single-stranded DNA viruses infect archaea, bacteria, and eukaryotic organisms. The relatively recent emergence of single-stranded DNA viruses, such as chicken anemia virus (CAV) and porcine circovirus 2 (PCV2), as serious pathogens of eukaryotes is due more to growing awareness than to the appearance of new pathogens or alteration of existing pathogens. In the case of the ubiquitous human circular single-stranded DNA virus family Anelloviridae, there is still no convincing direct causal relation to any specific disease. However, infections may play a role in autoimmunity by changing the homeostatic balance of proinflammatory cytokines and the human immune system, indirectly affecting the severity of diseases caused by other pathogens. Infections with CAV (family Anelloviridae, genus Gyrovirus) and PCV2 (family Circoviridae, genus Circovirus) are presented here because they are immunosuppressive and affect health in domesticated animals. CAV shares genomic organization, genomic orientation, and common features of major proteins with human anelloviruses, and PCV2 DNA may be present in human food and vaccines.
Topics: Anelloviridae; Animals; Animals, Domestic; Archaea; Autoimmunity; Bacteria; Chicken anemia virus; Circoviridae Infections; Circovirus; DNA Virus Infections; DNA Viruses; DNA, Circular; DNA, Single-Stranded; DNA, Viral; Genome, Viral; Humans; Swine; Swine Diseases
PubMed: 28715975
DOI: 10.1146/annurev-virology-101416-041953