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Special Issue "Virus Bioinformatics"

A special issue of Viruses (ISSN 1999-4915).

Deadline for manuscript submissions: closed (31 March 2019).

Special Issue Editors

Guest Editor
Prof. Dr. Manja Marz

The European Virus Bioinformatics Center and Friedrich Schiller University, Jena, Germany
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Interests: high throughput sequencing analysis; bioinformatic analysis and system biology of viruses; comparative genomics; identification and annotation of non-coding RNAs; coevolution of proteins and RNAs; algorithmic bioinformatics
Guest Editor
Prof. Dr. habil. Bashar Ibrahim

The European Virus Bioinformatics Center, Jena, Germany and Gulf University for Science and Technology, Hawally, Kuwait
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Interests: mathematical and computational systems biology; multiscale and unconventional modelling, simulation, and analysis of complex systems
Guest Editor
Dr. Franziska Hufsky

The European Virus Bioinformatics Center and Friedrich Schiller University Jena, Germany
Website | E-Mail
Interests: computational metabolomics and mass spectrometry; algorithms in bioinformatics; virus bioinformatics
Guest Editor
Prof. Dr. David L. Robertson

MRC-University of Glasgow Centre for Virus Research, Scotland
Website | E-Mail
Interests: computational and evolutionary biology; viral and molecular evolution; genomics and disease

Special Issue Information

Dear Colleagues,

This Special Issue is related to the Third Annual Meeting of the European Virus Bioinformatics Center which will be held at the University of Glasgow, Glasgow, UK, in March, 2019.

Bioinformatics is focusing on bacteria and eukaryotic model organisms while virologists have an urgent need of virus-specific bioinformatical tools. Apart from pioneering work on HIV-1, HCV and influenza, these two communities have interacted surprisingly sporadically.

This special issue will present articles covering computational approaches in virology, and we welcome any contributions within this cross-disciplinary field. Sub-topics include (but are not limited to): Virus detection, annotation, and comparison; quasispecies, phylogeny, and cophylogeny; virus–host interaction and replication; as well as drug design. We aim with this Special Issue for excellence and innovation with deep impact for a better, healthy world.

Hence, the Special Issue is open to all researchers working on the boundaries between bioinformatics and virology.

Papers are welcome as original research articles, as well as review papers dealing with recent advancements and current understanding of computational technologies aspects of virology.

All papers should be submitted online at https://www.mdpi.com/journal/viruses. Please select the correct Special Issue when submitting your paper to Viruses.

Prof. Dr. Manja Marz
PD Dr. habil. Bashar Ibrahim
Dr. Franziska Hufsky
Prof. Dr. David L. Robertson
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • specific bioinformatical tools to be applied in virology
  • computational modeling for viruses
  • virus detection, annotation, and comparison
  • quasispecies, phylogeny, and cophylogeny
  • virus-host interaction and replication
  • drug design

Published Papers (18 papers)

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Open AccessArticle
Purple: A Computational Workflow for Strategic Selection of Peptides for Viral Diagnostics Using MS-Based Targeted Proteomics
Viruses 2019, 11(6), 536; https://doi.org/10.3390/v11060536
Received: 19 March 2019 / Revised: 3 June 2019 / Accepted: 4 June 2019 / Published: 8 June 2019
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Abstract
Emerging virus diseases present a global threat to public health. To detect viral pathogens in time-critical scenarios, accurate and fast diagnostic assays are required. Such assays can now be established using mass spectrometry-based targeted proteomics, by which viral proteins can be rapidly detected [...] Read more.
Emerging virus diseases present a global threat to public health. To detect viral pathogens in time-critical scenarios, accurate and fast diagnostic assays are required. Such assays can now be established using mass spectrometry-based targeted proteomics, by which viral proteins can be rapidly detected from complex samples down to the strain-level with high sensitivity and reproducibility. Developing such targeted assays involves tedious steps of peptide candidate selection, peptide synthesis, and assay optimization. Peptide selection requires extensive preprocessing by comparing candidate peptides against a large search space of background proteins. Here we present Purple (Picking unique relevant peptides for viral experiments), a software tool for selecting target-specific peptide candidates directly from given proteome sequence data. It comes with an intuitive graphical user interface, various parameter options and a threshold-based filtering strategy for homologous sequences. Purple enables peptide candidate selection across various taxonomic levels and filtering against backgrounds of varying complexity. Its functionality is demonstrated using data from different virus species and strains. Our software enables to build taxon-specific targeted assays and paves the way to time-efficient and robust viral diagnostics using targeted proteomics. Full article
(This article belongs to the Special Issue Virus Bioinformatics)
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Open AccessArticle
Evaluation of Sequencing Library Preparation Protocols for Viral Metagenomic Analysis from Pristine Aquifer Groundwaters
Viruses 2019, 11(6), 484; https://doi.org/10.3390/v11060484
Received: 31 March 2019 / Revised: 26 May 2019 / Accepted: 27 May 2019 / Published: 28 May 2019
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Abstract
Viral ecology of terrestrial habitats is yet-to be extensively explored, in particular the terrestrial subsurface. One problem in obtaining viral sequences from groundwater aquifer samples is the relatively low amount of virus particles. As a result, the amount of extracted DNA may not [...] Read more.
Viral ecology of terrestrial habitats is yet-to be extensively explored, in particular the terrestrial subsurface. One problem in obtaining viral sequences from groundwater aquifer samples is the relatively low amount of virus particles. As a result, the amount of extracted DNA may not be sufficient for direct sequencing of such samples. Here we compared three DNA amplification methods to enrich viral DNA from three pristine limestone aquifer assemblages of the Hainich Critical Zone Exploratory to evaluate potential bias created by the different amplification methods as determined by viral metagenomics. Linker amplification shotgun libraries resulted in lowest redundancy among the sequencing reads and showed the highest diversity, while multiple displacement amplification produced the highest number of contigs with the longest average contig size, suggesting a combination of these two methods is suitable for the successful enrichment of viral DNA from pristine groundwater samples. In total, we identified 27,173, 5,886 and 32,613 viral contigs from the three samples from which 11.92 to 18.65% could be assigned to taxonomy using blast. Among these, members of the Caudovirales order were the most abundant group (52.20 to 69.12%) dominated by Myoviridae and Siphoviridae. Those, and the high number of unknown viral sequences, substantially expand the known virosphere. Full article
(This article belongs to the Special Issue Virus Bioinformatics)
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Open AccessArticle
Structure and Hierarchy of Influenza Virus Models Revealed by Reaction Network Analysis
Viruses 2019, 11(5), 449; https://doi.org/10.3390/v11050449
Received: 26 March 2019 / Revised: 8 May 2019 / Accepted: 11 May 2019 / Published: 16 May 2019
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Abstract
Influenza A virus is recognized today as one of the most challenging viruses that threatens both human and animal health worldwide. Understanding the control mechanisms of influenza infection and dynamics is crucial and could result in effective future treatment strategies. Many kinetic models [...] Read more.
Influenza A virus is recognized today as one of the most challenging viruses that threatens both human and animal health worldwide. Understanding the control mechanisms of influenza infection and dynamics is crucial and could result in effective future treatment strategies. Many kinetic models based on differential equations have been developed in recent decades to capture viral dynamics within a host. These models differ in their complexity in terms of number of species elements and number of reactions. Here, we present a new approach to understanding the overall structure of twelve influenza A virus infection models and their relationship to each other. To this end, we apply chemical organization theory to obtain a hierarchical decomposition of the models into chemical organizations. The decomposition is based on the model structure (reaction rules) but is independent of kinetic details such as rate constants. We found different types of model structures ranging from two to eight organizations. Furthermore, the model’s organizations imply a partial order among models entailing a hierarchy of model, revealing a high model diversity with respect to their long-term behavior. Our methods and results can be helpful in model development and model integration, also beyond the influenza area. Full article
(This article belongs to the Special Issue Virus Bioinformatics)
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Open AccessArticle
The Third Annual Meeting of the European Virus Bioinformatics Center
Viruses 2019, 11(5), 420; https://doi.org/10.3390/v11050420
Received: 28 April 2019 / Accepted: 29 April 2019 / Published: 5 May 2019
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Abstract
The Third Annual Meeting of the European Virus Bioinformatics Center (EVBC) took place in Glasgow, United Kingdom, 28–29 March 2019. Virus bioinformatics has become central to virology research, and advances in bioinformatics have led to improved approaches to investigate viral infections and outbreaks, [...] Read more.
The Third Annual Meeting of the European Virus Bioinformatics Center (EVBC) took place in Glasgow, United Kingdom, 28–29 March 2019. Virus bioinformatics has become central to virology research, and advances in bioinformatics have led to improved approaches to investigate viral infections and outbreaks, being successfully used to detect, control, and treat infections of humans and animals. This active field of research has attracted approximately 110 experts in virology and bioinformatics/computational biology from Europe and other parts of the world to attend the two-day meeting in Glasgow to increase scientific exchange between laboratory- and computer-based researchers. The meeting was held at the McIntyre Building of the University of Glasgow; a perfect location, as it was originally built to be a place for “rubbing your brains with those of other people”, as Rector Stanley Baldwin described it. The goal of the meeting was to provide a meaningful and interactive scientific environment to promote discussion and collaboration and to inspire and suggest new research directions and questions. The meeting featured eight invited and twelve contributed talks, on the four main topics: (1) systems virology, (2) virus-host interactions and the virome, (3) virus classification and evolution and (4) epidemiology, surveillance and evolution. Further, the meeting featured 34 oral poster presentations, all of which focused on specific areas of virus bioinformatics. This report summarizes the main research findings and highlights presented at the meeting. Full article
(This article belongs to the Special Issue Virus Bioinformatics)
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Open AccessArticle
Conserved Secondary Structures in Viral mRNAs
Viruses 2019, 11(5), 401; https://doi.org/10.3390/v11050401
Received: 30 March 2019 / Revised: 23 April 2019 / Accepted: 26 April 2019 / Published: 29 April 2019
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Abstract
RNA secondary structure in untranslated and protein coding regions has been shown to play an important role in regulatory processes and the viral replication cycle. While structures in non-coding regions have been investigated extensively, a thorough overview of the structural repertoire of protein [...] Read more.
RNA secondary structure in untranslated and protein coding regions has been shown to play an important role in regulatory processes and the viral replication cycle. While structures in non-coding regions have been investigated extensively, a thorough overview of the structural repertoire of protein coding mRNAs, especially for viruses, is lacking. Secondary structure prediction of large molecules, such as long mRNAs remains a challenging task, as the contingent of structures a sequence can theoretically fold into grows exponentially with sequence length. We applied a structure prediction pipeline to Viral Orthologous Groups that first identifies the local boundaries of potentially structured regions and subsequently predicts their functional importance. Using this procedure, the orthologous groups were split into structurally homogenous subgroups, which we call subVOGs. This is the first compilation of potentially functional conserved RNA structures in viral coding regions, covering the complete RefSeq viral database. We were able to recover structural elements from previous studies and discovered a variety of novel structured regions. The subVOGs are available through our web resource RNASIV (RNA structure in viruses). Full article
(This article belongs to the Special Issue Virus Bioinformatics)
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Open AccessArticle
RNAseq Analysis Reveals Virus Diversity within Hawaiian Apiary Insect Communities
Viruses 2019, 11(5), 397; https://doi.org/10.3390/v11050397
Received: 15 March 2019 / Revised: 11 April 2019 / Accepted: 24 April 2019 / Published: 27 April 2019
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Abstract
Deformed wing virus (DWV) is the most abundant viral pathogen of honey bees and has been associated with large-scale colony losses. DWV and other bee-associated RNA viruses are generalists capable of infecting diverse hosts. Here, we used RNAseq analysis to test the hypothesis [...] Read more.
Deformed wing virus (DWV) is the most abundant viral pathogen of honey bees and has been associated with large-scale colony losses. DWV and other bee-associated RNA viruses are generalists capable of infecting diverse hosts. Here, we used RNAseq analysis to test the hypothesis that due to the frequency of interactions, a range of apiary pest species would become infected with DWV and/or other honey bee-associated viruses. We confirmed that DWV-A was the most prevalent virus in the apiary, with genetically similar sequences circulating in the apiary pests, suggesting frequent inter-species transmission. In addition, different proportions of the three DWV master variants as indicated by BLAST analysis and genome coverage plots revealed interesting DWV-species groupings. We also observed that new genomic recombinants were formed by the DWV master variants, which are likely adapted to replicate in different host species. Species groupings also applied when considering other viruses, many of which were widespread in the apiaries. In social wasps, samples were grouped further by site, which potentially also influenced viral load. Thus, the apiary invertebrate community has the potential to act as reservoirs of honey bee-associated viruses, highlighting the importance of considering the wider community in the apiary when considering honey bee health. Full article
(This article belongs to the Special Issue Virus Bioinformatics)
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Open AccessArticle
The Utility of Data Transformation for Alignment, De Novo Assembly and Classification of Short Read Virus Sequences
Viruses 2019, 11(5), 394; https://doi.org/10.3390/v11050394
Received: 30 March 2019 / Revised: 19 April 2019 / Accepted: 22 April 2019 / Published: 26 April 2019
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Abstract
Advances in DNA sequencing technology are facilitating genomic analyses of unprecedented scope and scale, widening the gap between our abilities to generate and fully exploit biological sequence data. Comparable analytical challenges are encountered in other data-intensive fields involving sequential data, such as signal [...] Read more.
Advances in DNA sequencing technology are facilitating genomic analyses of unprecedented scope and scale, widening the gap between our abilities to generate and fully exploit biological sequence data. Comparable analytical challenges are encountered in other data-intensive fields involving sequential data, such as signal processing, in which dimensionality reduction (i.e., compression) methods are routinely used to lessen the computational burden of analyses. In this work, we explored the application of dimensionality reduction methods to numerically represent high-throughput sequence data for three important biological applications of virus sequence data: reference-based mapping, short sequence classification and de novo assembly. Leveraging highly compressed sequence transformations to accelerate sequence comparison, our approach yielded comparable accuracy to existing approaches, further demonstrating its suitability for sequences originating from diverse virus populations. We assessed the application of our methodology using both synthetic and real viral pathogen sequences. Our results show that the use of highly compressed sequence approximations can provide accurate results, with analytical performance retained and even enhanced through appropriate dimensionality reduction of sequence data. Full article
(This article belongs to the Special Issue Virus Bioinformatics)
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Open AccessArticle
Interpreting Viral Deep Sequencing Data with GLUE
Viruses 2019, 11(4), 323; https://doi.org/10.3390/v11040323
Received: 28 February 2019 / Revised: 13 March 2019 / Accepted: 14 March 2019 / Published: 3 April 2019
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Abstract
Using deep sequencing technologies such as Illumina’s platform, it is possible to obtain reads from the viral RNA population revealing the viral genome diversity within a single host. A range of software tools and pipelines can transform raw deep sequencing reads into Sequence [...] Read more.
Using deep sequencing technologies such as Illumina’s platform, it is possible to obtain reads from the viral RNA population revealing the viral genome diversity within a single host. A range of software tools and pipelines can transform raw deep sequencing reads into Sequence Alignment Mapping (SAM) files. We propose that interpretation tools should process these SAM files, directly translating individual reads to amino acids in order to extract statistics of interest such as the proportion of different amino acid residues at specific sites. This preserves per-read linkage between nucleotide variants at different positions within a codon location. The samReporter is a subsystem of the GLUE software toolkit which follows this direct read translation approach in its processing of SAM files. We test samReporter on a deep sequencing dataset obtained from a cohort of 241 UK HCV patients for whom prior treatment with direct-acting antivirals has failed; deep sequencing and resistance testing have been suggested to be of clinical use in this context. We compared the polymorphism interpretation results of the samReporter against an approach that does not preserve per-read linkage. We found that the samReporter was able to properly interpret the sequence data at resistance-associated locations in nine patients where the alternative approach was equivocal. In three cases, the samReporter confirmed that resistance or an atypical substitution was present at NS5A position 30. In three further cases, it confirmed that the sofosbuvir-resistant NS5B substitution S282T was absent. This suggests the direct read translation approach implemented is of value for interpreting viral deep sequencing data. Full article
(This article belongs to the Special Issue Virus Bioinformatics)
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Open AccessArticle
Protein Structure-Guided Hidden Markov Models (HMMs) as A Powerful Method in the Detection of Ancestral Endogenous Viral Elements
Viruses 2019, 11(4), 320; https://doi.org/10.3390/v11040320
Received: 29 January 2019 / Revised: 23 March 2019 / Accepted: 27 March 2019 / Published: 2 April 2019
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Abstract
It has been believed for a long time that the transfer and fixation of genetic material from RNA viruses to eukaryote genomes is very unlikely. However, during the last decade, there have been several cases in which “virus-to-host” gene transfer from various viral [...] Read more.
It has been believed for a long time that the transfer and fixation of genetic material from RNA viruses to eukaryote genomes is very unlikely. However, during the last decade, there have been several cases in which “virus-to-host” gene transfer from various viral families into various eukaryotic phyla have been described. These transfers have been identified by sequence similarity, which may disappear very quickly, especially in the case of RNA viruses. However, compared to sequences, protein structure is known to be more conserved. Applying protein structure-guided protein domain-specific Hidden Markov Models, we detected homologues of the Virgaviridae capsid protein in Schizophora flies. Further data analysis supported “virus-to-host” transfer into Schizophora ancestors as a single transfer event. This transfer was not identifiable by BLAST or by other methods we applied. Our data show that structure-guided Hidden Markov Models should be used to detect ancestral virus-to-host transfers. Full article
(This article belongs to the Special Issue Virus Bioinformatics)
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Open AccessArticle
Functional RNA Structures in the 3′UTR of Tick-Borne, Insect-Specific and No-Known-Vector Flaviviruses
Viruses 2019, 11(3), 298; https://doi.org/10.3390/v11030298
Received: 1 March 2019 / Revised: 19 March 2019 / Accepted: 20 March 2019 / Published: 24 March 2019
Cited by 2 | PDF Full-text (745 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Untranslated regions (UTRs) of flaviviruses contain a large number of RNA structural elements involved in mediating the viral life cycle, including cyclisation, replication, and encapsidation. Here we report on a comparative genomics approach to characterize evolutionarily conserved RNAs in the 3UTR [...] Read more.
Untranslated regions (UTRs) of flaviviruses contain a large number of RNA structural elements involved in mediating the viral life cycle, including cyclisation, replication, and encapsidation. Here we report on a comparative genomics approach to characterize evolutionarily conserved RNAs in the 3 UTR of tick-borne, insect-specific and no-known-vector flaviviruses in silico. Our data support the wide distribution of previously experimentally characterized exoribonuclease resistant RNAs (xrRNAs) within tick-borne and no-known-vector flaviviruses and provide evidence for the existence of a cascade of duplicated RNA structures within insect-specific flaviviruses. On a broader scale, our findings indicate that viral 3 UTRs represent a flexible scaffold for evolution to come up with novel xrRNAs. Full article
(This article belongs to the Special Issue Virus Bioinformatics)
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Open AccessArticle
Gram-Positive Bacteria-Like DNA Binding Machineries Involved in Replication Initiation and Termination Mechanisms of Mimivirus
Viruses 2019, 11(3), 267; https://doi.org/10.3390/v11030267
Received: 29 January 2019 / Revised: 14 March 2019 / Accepted: 14 March 2019 / Published: 17 March 2019
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Abstract
The detailed mechanisms of replication initiation, termination and segregation events were not yet known in Acanthamoeba polyphaga mimivirus (APMV). Here, we show detailed bioinformatics-based analyses of chromosomal replication in APMV from initiation to termination mediated by proteins bound to specific DNA sequences. Using [...] Read more.
The detailed mechanisms of replication initiation, termination and segregation events were not yet known in Acanthamoeba polyphaga mimivirus (APMV). Here, we show detailed bioinformatics-based analyses of chromosomal replication in APMV from initiation to termination mediated by proteins bound to specific DNA sequences. Using GC/AT skew and coding sequence skew analysis, we estimated that the replication origin is located at 382 kb in the APMV genome. We performed homology-modeling analysis of the gamma domain of APMV-FtsK (DNA translocase coordinating chromosome segregation) related to FtsK-orienting polar sequences (KOPS) binding, suggesting that there was an insertion in the gamma domain which maintains the structure of the DNA binding motif. Furthermore, UvrD/Rep-like helicase in APMV was homologous to Bacillus subtilis AddA, while the chi-like quartet sequence 5′-CCGC-3′ was frequently found in the estimated ori region, suggesting that chromosomal replication of APMV is initiated via chi-like sequence recognition by UvrD/Rep-like helicase. Therefore, the replication initiation, termination and segregation of APMV are presumably mediated by DNA repair machineries derived from gram-positive bacteria. Moreover, the other frequently observed quartet sequence 5′-CGGC-3′ in the ori region was homologous to the mitochondrial signal sequence of replication initiation, while the comparison of quartet sequence composition in APMV/Rickettsia-genome showed significantly similar values, suggesting that APMV also conserves the mitochondrial replication system acquired from an ancestral genome of mitochondria during eukaryogenesis. Full article
(This article belongs to the Special Issue Virus Bioinformatics)
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Open AccessArticle
The Transcriptional Landscape of Marek’s Disease Virus in Primary Chicken B Cells Reveals Novel Splice Variants and Genes
Viruses 2019, 11(3), 264; https://doi.org/10.3390/v11030264
Received: 18 February 2019 / Revised: 12 March 2019 / Accepted: 13 March 2019 / Published: 16 March 2019
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Abstract
Marek’s disease virus (MDV) is an oncogenic alphaherpesvirus that infects chickens and poses a serious threat to poultry health. In infected animals, MDV efficiently replicates in B cells in various lymphoid organs. Despite many years of research, the viral transcriptome in primary target [...] Read more.
Marek’s disease virus (MDV) is an oncogenic alphaherpesvirus that infects chickens and poses a serious threat to poultry health. In infected animals, MDV efficiently replicates in B cells in various lymphoid organs. Despite many years of research, the viral transcriptome in primary target cells of MDV remained unknown. In this study, we uncovered the transcriptional landscape of the very virulent RB1B strain and the attenuated CVI988/Rispens vaccine strain in primary chicken B cells using high-throughput RNA-sequencing. Our data confirmed the expression of known genes, but also identified a novel spliced MDV gene in the unique short region of the genome. Furthermore, de novo transcriptome assembly revealed extensive splicing of viral genes resulting in coding and non-coding RNA transcripts. A novel splicing isoform of MDV UL15 could also be confirmed by mass spectrometry and RT-PCR. In addition, we could demonstrate that the associated transcriptional motifs are highly conserved and closely resembled those of the host transcriptional machinery. Taken together, our data allow a comprehensive re-annotation of the MDV genome with novel genes and splice variants that could be targeted in further research on MDV replication and tumorigenesis. Full article
(This article belongs to the Special Issue Virus Bioinformatics)
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Open AccessArticle
A Needle in A Haystack: Tracing Bivalve-Associated Viruses in High-Throughput Transcriptomic Data
Viruses 2019, 11(3), 205; https://doi.org/10.3390/v11030205
Received: 1 February 2019 / Revised: 25 February 2019 / Accepted: 25 February 2019 / Published: 1 March 2019
Cited by 1 | PDF Full-text (2254 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Bivalve mollusks thrive in environments rich in microorganisms, such as estuarine and coastal waters, and they tend to accumulate various particles, including viruses. However, the current knowledge on mollusk viruses is mainly centered on few pathogenic viruses, whereas a general view of bivalve-associated [...] Read more.
Bivalve mollusks thrive in environments rich in microorganisms, such as estuarine and coastal waters, and they tend to accumulate various particles, including viruses. However, the current knowledge on mollusk viruses is mainly centered on few pathogenic viruses, whereas a general view of bivalve-associated viromes is lacking. This study was designed to explore the viral abundance and diversity in bivalve mollusks using transcriptomic datasets. From analyzing RNA-seq data of 58 bivalve species, we have reconstructed 26 nearly complete and over 413 partial RNA virus genomes. Although 96.4% of the predicted viral proteins refer to new viruses, some sequences belong to viruses associated with bivalve species or other marine invertebrates. We considered short non-coding RNAs (sncRNA) and post-transcriptional modifications occurring specifically on viral RNAs as tools for virus host-assignment. We could not identify virus-derived small RNAs in sncRNA reads obtained from the oyster sample richest in viral reads. Single Nucleotide Polymorphism (SNP) analysis revealed 938 A-to-G substitutions occurring on the 26 identified RNA viruses, preferentially impacting the AA di-nucleotide motif. Under-representation analysis revealed that the AA motif is under-represented in these bivalve-associated viruses. These findings improve our understanding of bivalve viromes, and set the stage for targeted investigations on the specificity and dynamics of identified viruses. Full article
(This article belongs to the Special Issue Virus Bioinformatics)
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Open AccessArticle
Exploring the Papillomaviral Proteome to Identify Potential Candidates for a Chimeric Vaccine against Cervix Papilloma Using Immunomics and Computational Structural Vaccinology
Viruses 2019, 11(1), 63; https://doi.org/10.3390/v11010063
Received: 29 November 2018 / Revised: 3 January 2019 / Accepted: 10 January 2019 / Published: 15 January 2019
Cited by 1 | PDF Full-text (17842 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The human papillomavirus (HPV) 58 is considered to be the second most predominant genotype in cervical cancer incidents in China. HPV type-restriction, non-targeted delivery, and the highcost of existing vaccines necessitate continuing research on the HPV vaccine. We aimed to explore the papillomaviral [...] Read more.
The human papillomavirus (HPV) 58 is considered to be the second most predominant genotype in cervical cancer incidents in China. HPV type-restriction, non-targeted delivery, and the highcost of existing vaccines necessitate continuing research on the HPV vaccine. We aimed to explore the papillomaviral proteome in order to identify potential candidates for a chimeric vaccine against cervix papilloma using computational immunology and structural vaccinology approaches. Two overlapped epitope segments (23–36) and (29–42) from the N-terminal region of the HPV58 minor capsid protein L2 are selected as capable of inducing both cellular and humoral immunity. In total, 318 amino acid lengths of the vaccine construct SGD58 contain adjuvants (Flagellin and RS09), two Th epitopes, and linkers. SGD58 is a stable protein that is soluble, antigenic, and non-allergenic. Homology modeling and the structural refinement of the best models of SGD58 and TLR5 found 96.8% and 93.9% favored regions in Rampage, respectively. The docking results demonstrated a HADDOCK score of −62.5 ± 7.6, the binding energy (−30 kcal/mol) and 44 interacting amino acid residues between SGD58-TLR5 complex. The docked complex are stable in 100 ns of simulation. The coding sequences of SGD58 also show elevated gene expression in Escherichia coli with 1.0 codon adaptation index and 59.92% glycine-cysteine content. We conclude that SGD58 may prompt the creation a vaccine against cervix papilloma. Full article
(This article belongs to the Special Issue Virus Bioinformatics)
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Open AccessArticle
Proteogenomics Uncovers Critical Elements of Host Response in Bovine Soft Palate Epithelial Cells Following In Vitro Infection with Foot-And-Mouth Disease Virus
Viruses 2019, 11(1), 53; https://doi.org/10.3390/v11010053
Received: 20 December 2018 / Revised: 8 January 2019 / Accepted: 11 January 2019 / Published: 12 January 2019
Cited by 1 | PDF Full-text (3945 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Foot-and-mouth disease (FMD) is the most devastating disease of cloven-hoofed livestock, with a crippling economic burden in endemic areas and immense costs associated with outbreaks in free countries. Foot-and-mouth disease virus (FMDV), a picornavirus, will spread rapidly in naïve populations, reaching morbidity rates [...] Read more.
Foot-and-mouth disease (FMD) is the most devastating disease of cloven-hoofed livestock, with a crippling economic burden in endemic areas and immense costs associated with outbreaks in free countries. Foot-and-mouth disease virus (FMDV), a picornavirus, will spread rapidly in naïve populations, reaching morbidity rates of up to 100% in cattle. Even after recovery, over 50% of cattle remain subclinically infected and infectious virus can be recovered from the nasopharynx. The pathogen and host factors that contribute to FMDV persistence are currently not understood. Using for the first time primary bovine soft palate multilayers in combination with proteogenomics, we analyzed the transcriptional responses during acute and persistent FMDV infection. During the acute phase viral RNA and protein was detectable in large quantities and in response hundreds of interferon-stimulated genes (ISG) were overexpressed, mediating antiviral activity and apoptosis. Although the number of pro-apoptotic ISGs and the extent of their regulation decreased during persistence, some ISGs with antiviral activity were still highly expressed at that stage. This indicates a long-lasting but ultimately ineffective stimulation of ISGs during FMDV persistence. Furthermore, downregulation of relevant genes suggests an interference with the extracellular matrix that may contribute to the skewed virus-host equilibrium in soft palate epithelial cells. Full article
(This article belongs to the Special Issue Virus Bioinformatics)
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Open AccessArticle
Base-By-Base Version 3: New Comparative Tools for Large Virus Genomes
Viruses 2018, 10(11), 637; https://doi.org/10.3390/v10110637
Received: 25 October 2018 / Revised: 10 November 2018 / Accepted: 13 November 2018 / Published: 15 November 2018
Cited by 1 | PDF Full-text (1324 KB) | HTML Full-text | XML Full-text
Abstract
Base-By-Base is a comprehensive tool for the creation and editing of multiple sequence alignments that is coded in Java and runs on multiple platforms. It can be used with gene and protein sequences as well as with large viral genomes, which themselves can [...] Read more.
Base-By-Base is a comprehensive tool for the creation and editing of multiple sequence alignments that is coded in Java and runs on multiple platforms. It can be used with gene and protein sequences as well as with large viral genomes, which themselves can contain gene annotations. This report describes new features added to Base-By-Base over the last 7 years. The two most significant additions are: (1) The recoding and inclusion of “consensus-degenerate hybrid oligonucleotide primers” (CODEHOP), a popular tool for the design of degenerate primers from a multiple sequence alignment of proteins; and (2) the ability to perform fuzzy searches within the columns of sequence data in multiple sequence alignments to determine the distribution of sequence variants among the sequences. The intuitive interface focuses on the presentation of results in easily understood visualizations and providing the ability to annotate the sequences in a multiple alignment with analytic and user data. Full article
(This article belongs to the Special Issue Virus Bioinformatics)
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Review

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Open AccessReview
Giant Viruses—Big Surprises
Viruses 2019, 11(5), 404; https://doi.org/10.3390/v11050404
Received: 22 March 2019 / Revised: 17 April 2019 / Accepted: 23 April 2019 / Published: 30 April 2019
Cited by 1 | PDF Full-text (1529 KB) | HTML Full-text | XML Full-text
Abstract
Viruses are the most prevalent infectious agents, populating almost every ecosystem on earth. Most viruses carry only a handful of genes supporting their replication and the production of capsids. It came as a great surprise in 2003 when the first giant virus was [...] Read more.
Viruses are the most prevalent infectious agents, populating almost every ecosystem on earth. Most viruses carry only a handful of genes supporting their replication and the production of capsids. It came as a great surprise in 2003 when the first giant virus was discovered and found to have a >1 Mbp genome encoding almost a thousand proteins. Following this first discovery, dozens of giant virus strains across several viral families have been reported. Here, we provide an updated quantitative and qualitative view on giant viruses and elaborate on their shared and variable features. We review the complexity of giant viral proteomes, which include functions traditionally associated only with cellular organisms. These unprecedented functions include components of the translation machinery, DNA maintenance, and metabolic enzymes. We discuss the possible underlying evolutionary processes and mechanisms that might have shaped the diversity of giant viruses and their genomes, highlighting their remarkable capacity to hijack genes and genomic sequences from their hosts and environments. This leads us to examine prominent theories regarding the origin of giant viruses. Finally, we present the emerging ecological view of giant viruses, found across widespread habitats and ecological systems, with respect to the environment and human health. Full article
(This article belongs to the Special Issue Virus Bioinformatics)
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Other

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Open AccessTechnical Note
QuantIF: An ImageJ Macro to Automatically Determine the Percentage of Infected Cells after Immunofluorescence
Viruses 2019, 11(2), 165; https://doi.org/10.3390/v11020165
Received: 21 January 2019 / Revised: 12 February 2019 / Accepted: 17 February 2019 / Published: 19 February 2019
PDF Full-text (1520 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Counting labeled cells, after immunofluorescence or expression of a genetically fluorescent reporter protein, is frequently used to quantify viral infection. However, this can be very tedious without a high content screening apparatus. For this reason, we have developed QuantIF, an ImageJ macro that [...] Read more.
Counting labeled cells, after immunofluorescence or expression of a genetically fluorescent reporter protein, is frequently used to quantify viral infection. However, this can be very tedious without a high content screening apparatus. For this reason, we have developed QuantIF, an ImageJ macro that automatically determines the total number of cells and the number of labeled cells from two images of the same field, using DAPI- and specific-stainings, respectively. QuantIF can automatically analyze hundreds of images, taking approximately one second for each field. It is freely available as supplementary data online at MDPI.com and has been developed using ImageJ, a free image processing program that can run on any computer with a Java virtual machine, which is distributed for Windows, Mac, and Linux. It is routinely used in our labs to quantify viral infections in vitro, but can easily be used for other applications that require quantification of labeled cells. Full article
(This article belongs to the Special Issue Virus Bioinformatics)
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