Viruses and Bioinformatics from Virology.uvic.ca
88.0K views | +13 today
Follow
Viruses and Bioinformatics from Virology.uvic.ca
Virus and bioinformatics articles with some microbiology and immunology thrown in for good measure
Your new post is loading...
Your new post is loading...
Scooped by Cindy
Scoop.it!

Development of Potent Antiviral Drugs Inspired by Viral Hexameric DNA-Packaging Motors with Revolving Mechanism

The intracellular parasitic nature of viruses and the emergence of antiviral drug resistance necessitate the development of new potent antiviral drugs. Recently, a method for developing potent inhibitory drugs by targeting biological machines with high stoichiometry and a sequential-action mechanism was described. Inspired by this finding, we reviewed the development of antiviral drugs targeting viral DNA-packaging motors. Inhibiting multisubunit targets with sequential actions resembles breaking one bulb in a series of Christmas lights, which turns off the entire string. Indeed, studies on viral DNA packaging might lead to the development of new antiviral drugs. Recent elucidation of the mechanism of the viral double-stranded DNA (dsDNA)-packaging motor with sequential one-way revolving motion will promote the development of potent antiviral drugs with high specificity and efficiency. Traditionally, biomotors have been classified into two categories: linear and rotation motors. Recently discovered was a third type of biomotor, including the viral DNA-packaging motor, beside the bacterial DNA translocases, that uses a revolving mechanism without rotation. By analogy, rotation resembles the Earth's rotation on its own axis, while revolving resembles the Earth's revolving around the Sun (see animations at http://rnanano.osu.edu/movie.html). Herein, we review the structures of viral dsDNA-packaging motors, the stoichiometries of motor components, and the motion mechanisms of the motors. All viral dsDNA-packaging motors, including those of dsDNA/dsRNA bacteriophages, adenoviruses, poxviruses, herpesviruses, mimiviruses, megaviruses, pandoraviruses, and pithoviruses, contain a high-stoichiometry machine composed of multiple components that work cooperatively and sequentially. Thus, it is an ideal target for potent drug development based on the power function of the stoichiometries of target complexes that work sequentially.
more...
No comment yet.
Scooped by Kathleen McLeod
Scoop.it!

Multiplexed Sequencing for Novel Viral Pathogens | Insight & Intelligence™ | GEN

Multiplexed Sequencing for Novel Viral Pathogens | Insight & Intelligence™ | GEN | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
As frequent travelers go, viruses are among the least welcome arrivals. They easily elude TSA agents, but they will have a harder time getting past the newer microarray platforms.
more...
No comment yet.
Scooped by Cindy
Scoop.it!

Evolution and molecular epidemiology of classical swine fever virus during a multi-annual outbreak amongst European wild boar

Classical swine fever is a viral disease of pigs that carries tremendous socio-economic impact. In outbreak situations, genetic typing is carried out for the purpose of molecular epidemiology in both domestic pigs and wild boar. These analyses are usually based on harmonized partial sequences. However, for high-resolution analyses towards the understanding of genetic variability and virus evolution, full-genome sequences are more appropriate. In this study, a unique set of representative virus strains was investigated that was collected during an outbreak in French free-ranging wild boar in the Vosges-du-Nord mountains between 2003 and 2007. Comparative sequence and evolutionary analyses of the nearly full-length sequences showed only slow evolution of classical swine fever virus strains over the years and no impact of vaccination on mutation rates. However, substitution rates varied amongst protein genes; furthermore, a spatial and temporal pattern could be observed whereby two separate clusters were formed that coincided with physical barriers.
more...
No comment yet.
Scooped by Cindy
Scoop.it!

Identification of Known and Novel Recurrent Viral Sequences in Data from Multiple Patients and Multiple Cancers

Virus discovery from high throughput sequencing data often follows a bottom-up approach where taxonomic annotation takes place prior to association to disease. Albeit effective in some cases, the approach fails to detect novel pathogens and remote variants not present in reference databases. We have developed a species independent pipeline that utilises sequence clustering for the identification of nucleotide sequences that co-occur across multiple sequencing data instances. We applied the workflow to 686 sequencing libraries from 252 cancer samples of different cancer and tissue types, 32 non-template controls, and 24 test samples. Recurrent sequences were statistically associated to biological, methodological or technical features with the aim to identify novel pathogens or plausible contaminants that may associate to a particular kit or method. We provide examples of identified inhabitants of the healthy tissue flora as well as experimental contaminants. Unmapped sequences that co-occur with high statistical significance potentially represent the unknown sequence space where novel pathogens can be identified.
more...
No comment yet.
Scooped by Cindy
Scoop.it!

VIRALpro: a tool to identify viral capsid and tail sequences

Previously, a tool called iVireons (Seguritan et al., 2012) has been introduced to detect structural proteins in phages—i.e. viruses that infect bacteria. The tool uses a single input—the average amino acid composition of the query sequence—which is fed into three classification neural networks: one for all structural proteins, one for tail proteins and one for capsid proteins. As stated by the authors, the tool performs well at detecting phage capsids, but its performance degrades when used to detect capsids in other viruses. The structural protein predictor has a reasonable sensitivity to all capsids, but its specificity is too low. To address these problems we develop VIRALpro using Support Vector Machines (SVM) and extended set of features to identify capsid (CAPSIDpro) and tail (TAILpro) sequences.
more...
No comment yet.
Scooped by Cindy
Scoop.it!

A phylogenomic data-driven exploration of viral origins and evolution

A phylogenomic data-driven exploration of viral origins and evolution | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it

-- What do you think?

 

"Despite the extremely reduced nature of viral proteomes, we established an ancient origin of the “viral supergroup” and the existence of widespread episodes of horizontal transfer of genetic information. ... 


... Phylogenomic analysis uncovered a universal tree of life and revealed that modern viruses reduced from multiple ancient cells that harbored segmented RNA genomes and coexisted with the ancestors of modern cells. The model for the origin and evolution of viruses and cells is backed by strong genomic and structural evidence and can be reconciled with existing models of viral evolution if one considers viruses to have originated from ancient cells and not from modern counterparts." 

more...
No comment yet.
Scooped by Chris Upton + helpers
Scoop.it!

Viruses might tame some algal blooms | Science News

Viruses might tame some algal blooms | Science News | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
The rapid demise of a giant, carbon-spewing algal bloom points to the influence of viral wranglers.
more...
No comment yet.
Scooped by burkesquires
Scoop.it!

Virus assembly and maturation: auto-regulation through allosteric molecular switches J Mol Biol. 2013

We generalize the concept of allostery from the traditional non-active-site control of enzymes to virus maturation. Virtually, all animal viruses transition from a procapsid noninfectious state to a mature infectious state. The procapsid contains an encoded chemical program that is executed following an environmental cue. We developed an exceptionally accessible virus system for the study of the activators of maturation and the downstream consequences that result in particle stability and infectivity. Nudaurelia capensis omega virus (NωV) is a T=4 icosahedral virus that undergoes a dramatic maturation in which the 490-Å spherical procapsid condenses to a 400-Å icosahedral-shaped capsid with associated specific auto-proteolysis and stabilization. Employing X-ray crystallography, time-resolved electron cryo-microscopy and hydrogen/deuterium exchange as well as biochemistry, it was possible to define the mechanisms of allosteric communication among the four quasi-equivalent subunits in the icosahedral asymmetric unit. These gene products undergo proteolysis at different rates, dependent on quaternary structure environment, while particle stability is conferred globally following only a few local subunit transitions. We show that there is a close similarity between the concepts of tensegrity (associated with geodesic domes and mechanical engineering) and allostery (associated with biochemical control mechanisms).

more...
No comment yet.
Scooped by C_Fleis
Scoop.it!

Emerging Microbes & Infections - Virus ecology: a gap between detection and prediction

Emerging Microbes & Infections - Virus ecology: a gap between detection and prediction | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
Emerging Microbes and Infections (EMI) is a new open access, fully peer-reviewed journal that will publish the best and most interesting research in emerging microbes and infectious disease.

The past few months have yielded disconcerting news about viruses carried in mammalian reservoirs. What is the relevance of virus discoveries mushrooming in the literature? Will bats yield the next pandemic virus? Animal ecologists and virologists need to join forces.

 
more...
No comment yet.
Scooped by Marion Koopmans
Scoop.it!

Bedeviled by Dengue - Scientist (blog)

Bedeviled by Dengue - Scientist (blog) | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
Scientist (blog) Bedeviled by Dengue Scientist (blog) The cells enclose the viruses in a sac—a process called receptor-mediated endocytosis—that would normally digest the viral captives with enzymes in an acidic milieu, like a piece of food in the...
Chris Upton + helpers's insight:

Nice mini review, including the discussion on antibody-mediated effects on pathogenesis. I do miss the recent data on antibodies rendering immature particles infectious, work from University of Groningen scientist professor Jolande Smit

more...
No comment yet.
Scooped by Naomi Osborne
Scoop.it!

MicroMicrobe • Winter Viruses and How to Beat Them BBC2 aired...

Winter Viruses and How to Beat Them


BBC2 aired another informative program on viruses last night; if you missed it due to a clash with Miranda, you can still catch up on ‘Winter Viruses and How to Beat Them’.
more...
No comment yet.
Scooped by Chris Upton + helpers
Scoop.it!

Cold #viruses point the way to new #cancer therapies

Cold #viruses point the way to new #cancer therapies | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
Cold viruses generally get a bad rap -- which they've certainly earned -- but new findings by a team of scientists suggest that these viruses might also be a valuable ally in the fight against cancer.
more...
No comment yet.
Scooped by Chris Upton + helpers
Scoop.it!

Killers on the loose: the deadly viruses that threaten human survival

Killers on the loose: the deadly viruses that threaten human survival | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
Could the next big animal-human disease wipe us out?
more...
No comment yet.
Scooped by Cindy
Scoop.it!

Descriptive Statistics of the Genome: Phylogenetic Classification of Viruses | Abstract

The typical process for classifying and submitting a newly sequenced virus to the NCBI database involves two steps. First, a BLAST search is performed to determine likely family candidates. That is followed by checking the candidate families with the pairwise sequence alignment tool for similar species. The submitter's judgment is then used to determine the most likely species classification. The aim of this article is to show that this process can be automated into a fast, accurate, one-step process using the proposed alignment-free method and properly implemented machine learning techniques.

We present a new family of alignment-free vectorizations of the genome, the generalized vector, that maintains the speed of existing alignment-free methods while outperforming all available methods. This new alignment-free vectorization uses the frequency of genomic words (k-mers), as is done in the composition vector, and incorporates descriptive statistics of those k-mers' positional information, as inspired by the natural vector.

more...
No comment yet.
Scooped by Cindy
Scoop.it!

An Evolutionary View of the Arms Race between Protein Kinase R and Large DNA Viruses

To establish productive infections, viruses must counteract numerous cellular defenses that are poised to recognize viruses as nonself and to activate antiviral pathways. The opposing goals of host and viral factors lead to evolutionary arms races that can be illuminated by evolutionary and computational methods and tested in experimental models. Here we illustrate how this perspective has been contributing to our understanding of the interactions of the protein kinase R pathway with large DNA viruses.
more...
No comment yet.
Scooped by Cindy
Scoop.it!

Computational Clustering for Viral Reference Proteomes

Motivation: The enormous number of redundant sequenced genomes has hindered efforts to analyze and functionally annotate proteins. As the taxonomy of viruses is not uniformly defined, viral proteomes pose special challenges in this regard. Grouping viruses based on the similarity of their proteins at proteome scale can normalize against potential taxonomic nomenclature anomalies.

Results: We present Viral Reference Proteomes (Viral RPs), which are computed from complete virus proteomes within UniProtKB. Viral RPs based on 95%, 75%, 55%, 35% and 15% co-membership in proteome similarity based clusters are provided. Comparison of our computational Viral RPs with UniProt’s curator-selected Reference Proteomes indicates that the two sets are consistent and complementary. Furthermore, each Viral RP represents a cluster of virus proteomes that was consistent with virus or host taxonomy. We provide BLASTP search and FTP download of Viral RP protein sequences, and a browser to facilitate the visualization of Viral RPs.

Availability: http://proteininformationresource.org/rps/viruses/
more...
No comment yet.
Scooped by Cindy
Scoop.it!

DeNovo: virus-host sequence-based protein–protein interaction prediction

Can we predict protein–protein interactions (PPIs) of a novel virus with its host? Three major problems arise: the lack of known PPIs for that virus to learn from, the cost of learning about its proteins and the sequence dissimilarity among viral families that makes most methods inapplicable or inefficient. We develop DeNovo, a sequence-based negative sampling and machine learning framework that learns from PPIs of different viruses to predict for a novel one, exploiting the shared host proteins. We tested DeNovo on PPIs from different domains to assess generalization.
more...
No comment yet.
Scooped by Cindy
Scoop.it!

Features of the Antitumor Effect of Vaccinia Virus Lister Strain

Features of the Antitumor Effect of Vaccinia Virus Lister Strain | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
Oncolytic abilities of vaccinia virus (VACV) served as a basis for the development of various recombinants for treating cancer; however, “natural” oncolytic properties of the virus are not examined in detail. Our study was conducted to know how the genetically unmodified L-IVP strain of VACV produces its antitumor effect.
more...
No comment yet.
Scooped by Paul Kim
Scoop.it!

Ebola Doctor Shortage Eases as Volunteers Step Forward

Ebola Doctor Shortage Eases as Volunteers Step Forward | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
Even with the volunteers, experts say, there will be a long gap before hospitals can be fully staffed to care for the growing numbers of Ebola patients.
more...
No comment yet.
Scooped by C_Fleis
Scoop.it!

Herpes Virus Genome, The Pressure Is On

Abstract

 

Herpes simplex virus type 1 (HSV-1) packages its micrometers-long double-stranded DNA genome into a nanometer-scale protein shell, termed the capsid. Upon confinement within the capsid, neighboring DNA strands experience repulsive electrostatic and hydration forces as well as bending stress associated with the tight curvature required of packaged DNA. By osmotically suppressing DNA release from HSV-1 capsids, we provide the first experimental evidence of a high internal pressure of tens of atmospheres within a eukaryotic human virus, resulting from the confined genome. Furthermore, the ejection is progressively suppressed by increasing external osmotic pressures, which reveals that internal pressure is capable of powering ejection of the entire genome from the viral capsid. Despite billions of years of evolution separating eukaryotic viruses and bacteriophages, pressure-driven DNA ejection has been conserved. This suggests it is a key mechanism for viral infection and thus presents a new target for antiviral therapies.

more...
No comment yet.
Rescooped by Chris Upton + helpers from Virology News
Scoop.it!

Virophages, polintons, and transpovirons: a complex evolutionary network of diverse selfish genetic elements with different reproduction strategies

Virophages, polintons, and transpovirons: a complex evolutionary network of diverse selfish genetic elements with different reproduction strategies | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it

The results of the phylogenomic analysis of the virophages and related genetic elements are compatible with the concept of network-like evolution of the virus world and emphasize multiple evolutionary connections between bona fide viruses and other classes of capsid-less mobile elements.

Altogether, virophages, polintons, a distinct Tetrahymena transposable element Tlr1, transpovirons, adenoviruses, and some bacteriophages form a network of evolutionary relationships that is held together by overlapping sets of shared genes and appears to represent a distinct module in the vast total network of viruses and mobile elements.


Via Chad Smithson, Ed Rybicki
more...
Ed Rybicki's curator insight, May 24, 2013 9:26 AM

Blow your MINDS, virologists...deep relationships between phages, human viruses, satellite viruses and big DNA viruses - as well as with diverse mobile elements within genomes.

Ignacio López-Goñi's curator insight, May 25, 2013 3:50 AM

Apasionante: el tema se complica! 

Scooped by Chris Upton + helpers
Scoop.it!

The pathogenesis of dengue

The pathogenesis of dengue | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
Better understanding of the underlying mechanisms leading to severe dengue is crucial if we are to develop better treatments.
Chris Upton + helpers's insight:

From MicrobiologyBytes

more...
No comment yet.
Scooped by Kenzibit
Scoop.it!

Differential unfolded protein response during Chikungunya and Sindbis virus infection: CHIKV nsP4 suppresses eIF2alpha phosphorylation

Chikungunya (CHIKV) and Sindbis (SINV) are arboviruses belonging to the alphavirus genus within the Togaviridae family. They cause frequent epidemics of febrile illness and long-term arthralgic sequelae that affect millions of people each year.
more...
No comment yet.
Scooped by Nicolas Palopoli
Scoop.it!

Different Regions of the HPV-E7 and Ad-E1A Viral Oncoproteins Bind Competitively but through Distinct Mechanisms to the CH1 Transactivation Domain of p300 - Biochemistry (ACS Publications)

Different Regions of the HPV-E7 and Ad-E1A Viral Oncoproteins Bind Competitively but through Distinct Mechanisms to the CH1 Transactivation Domain of p300 - Biochemistry (ACS Publications) | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
Nicolas Palopoli's insight:

Two oncoproteins with different structures and from different viruses use distinct mechanisms to bind the same partner and disrupt its function.

more...
No comment yet.
Scooped by Chris Upton + helpers
Scoop.it!

Subversion of cytokine networks by virally encoded decoy receptors.

PubMed comprises more than 22 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
more...
No comment yet.