Viruses and Bioinformatics from Virology.uvic.ca
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Viruses and Bioinformatics from Virology.uvic.ca
Virus and bioinformatics articles with some microbiology and immunology thrown in for good measure
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Scooped by Torben Barsballe
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Completion of the entire hepatitis C virus life cycle in genetically humanized mice

More than 130 million people worldwide chronically infected with hepatitis C virus (HCV) are at risk of developing severe liver disease. Antiviral treatments are only partially effective against HCV infection, and a vaccine is not available. Development of more efficient therapies has been hampered by the lack of a small animal model. Building on the observation that CD81 and occludin (OCLN) comprise the minimal set of human factors required to render mouse cells permissive to HCV entry1, we previously showed that transient expression of these two human genes is sufficient to allow viral uptake into fully immunocompetent inbred mice2. Here we demonstrate that transgenic mice stably expressing human CD81 and OCLN also support HCV entry, but innate and adaptive immune responses restrict HCV infection in vivo. Blunting antiviral immunity in genetically humanized mice infected with HCV results in measurable viraemia over several weeks. In mice lacking the essential cellular co-factor cyclophilin A (CypA), HCV RNA replication is markedly diminished, providing genetic evidence that this process is faithfully recapitulated. Using a cell-based fluorescent reporter activated by the NS3-4A protease we visualize HCV infection in single hepatocytes in vivo. Persistently infected mice produce de novo infectious particles, which can be inhibited with directly acting antiviral drug treatment, thereby providing evidence for the completion of the entire HCV life cycle in inbred mice. This genetically humanized mouse model opens new opportunities to dissect genetically HCV infection in vivo and provides an important preclinical platform for testing and prioritizing drug candidates and may also have utility for evaluating vaccine efficacy.

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Learning from a Virus: Keeping Genes Under Wraps | UANews

Learning from a Virus: Keeping Genes Under Wraps | UANews | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
By studying how the human cytomegalovirus, or CMV, packages its genetic material during infection, an international collaboration of researchers has identified potential inroads for new therapies that could one day prevent birth defects and save...
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Hemagglutinin Stalk-Based Universal Vaccine Constructs Protect Against Group 2 Influenza A Viruses

Current influenza virus vaccines contain H1N1 (phylogenetic group 1 hemagglutinin), H3N2 (phylogenetic group 2 hemagglutinin) and influenza B virus components. These vaccines induce good protection against closely matched strains by predominantly eliciting antibodies against the membrane distal globular head domain of their respective viral hemagglutinins. This domain, however, undergoes rapid antigenic drift allowing the virus to escape neutralizing antibody responses. The membrane proximal stalk domain of the hemagglutinin is much more conserved as compared to the head domain. In recent years, a growing collection of antibodies that neutralize a broad range of influenza virus strains and subtypes by binding to this domain, has been isolated. Here we demonstrate that a vaccination strategy based on the stalk domain of the H3 hemagglutinin (group 2) induces in mice broadly neutralizing anti-stalk antibodies that are highly crossreactive to heterologous H3, H10, H14, H15 and H7 (derived from the novel Chinese H7N9 virus) hemagglutinins. Furthermore, we demonstrate that these antibodies confer broad protection against influenza viruses expressing various group 2 hemagglutinins including an H7 subtype. Through passive transfer experiments, we show that the protection is mainly mediated by neutralizing antibodies against the stalk domain. Our data suggest that in mice a vaccine strategy based on the hemagglutinin stalk domain can protect against viruses expressing divergent group 2 hemagglutinins.

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PLOS Pathogens: A Multi-targeted Drug Candidate with Dual Anti-HIV and Anti-HSV Activity

PLOS Pathogens: A Multi-targeted Drug Candidate with Dual Anti-HIV and Anti-HSV Activity | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it

Human immunodeficiency virus (HIV) infection is often accompanied by infection with other pathogens, in particular herpes simplex virus type 2 (HSV-2). The resulting coinfection is involved in a vicious circle of mutual facilitations. Therefore, an important task is to develop a compound that is highly potent against both viruses to suppress their transmission and replication.From molecules to physiology

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Genome editing: Improved technique makes it easier to add or delete genes in living cells

Genome editing: Improved technique makes it easier to add or delete genes in living cells | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it

Earlier this year, MIT researchers developed a way to easily and efficiently edit the genomes of living cells. Now, the researchers have discovered key factors that influence the accuracy of the system, an important step toward making it safer for potential use in humans, says Feng Zhang, leader of the research team. 

With this technology, scientists can deliver or disrupt multiple genes at once, raising the possibility of treating human disease by targeting malfunctioning genes. To help with that process, Zhang’s team, led by graduate students Patrick Hsu and David Scott, has now created a computer model that can identify the best genetic sequences to target a given gene.

“Using this, you will be able to identify ways to target almost every gene. Within every gene, there are hundreds of locations that can be edited, and this will help researchers narrow down which ones are better than others,” says Zhang, the W.M. Keck Assistant Professor in Biomedical Engineering at MIT and senior author of a paper describing the new model, appearing in the July 21 online edition of Nature Biotechnology.

The genome-editing system, known as CRISPR, exploits a protein-RNA complex that bacteria use to defend themselves from infection. The complex includes short RNA sequences bound to an enzyme called Cas9, which slices DNA. These RNA sequences are designed to target specific locations in the genome; when they encounter a match, Cas9 cuts the DNA. 



Via Dr. Stefan Gruenwald
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Rescooped by Kenzibit from Host Cell & Pathogen Interactions
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Going Viral—Fluorescent Probes to Image Viruses and Their Host Cell Interactions | Life Technologies

Going Viral—Fluorescent Probes to Image Viruses and Their Host Cell Interactions | Life Technologies | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
The overarching goal of viral research is to understand the interactions between virus and host cell in the context of infection.
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Rescooped by Chris Upton + helpers from "Biotech and Mol Bio"
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A Subway Map Of The Metabolism [Infographic] | Popular Science

A Subway Map Of The Metabolism [Infographic] | Popular Science | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it

Via Isabel Etayo, sonia ramos
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Rescooped by Chris Upton + helpers from Plant Pathogenomics
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PLOS Pathogens: Genomic Analysis of the Kiwifruit Pathogen Pseudomonas syringae pv. actinidiae Provides Insight into the Origins of an Emergent Plant Disease (2013)

PLOS Pathogens: Genomic Analysis of the Kiwifruit Pathogen Pseudomonas syringae pv. actinidiae Provides Insight into the Origins of an Emergent Plant Disease (2013) | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it

The origins of crop diseases are linked to domestication of plants. Most crops were domesticated centuries – even millennia – ago, thus limiting opportunity to understand the concomitant emergence of disease. Kiwifruit (Actinidia spp.) is an exception: domestication began in the 1930s with outbreaks of canker disease caused by P. syringae pv. actinidiae(Psa) first recorded in the 1980s. Based on SNP analyses of two circularized and 34 draft genomes, we show that Psa is comprised of distinct clades exhibiting negligible within-clade diversity, consistent with disease arising by independent samplings from a source population. Three clades correspond to their geographical source of isolation; a fourth, encompassing thePsa-V lineage responsible for the 2008 outbreak, is now globally distributed. Psa has an overall clonal population structure, however, genomes carry a marked signature of within-pathovar recombination. SNP analysis of Psa-V reveals hundreds of polymorphisms; however, most reside within PPHGI-1-like conjugative elements whose evolution is unlinked to the core genome. Removal of SNPs due to recombination yields an uninformative (star-like) phylogeny consistent with diversification of Psa-V from a single clone within the last ten years. Growth assays provide evidence of cultivar specificity, with rapid systemic movement of Psa-V inActinidia chinensis. Genomic comparisons show a dynamic genome with evidence of positive selection on type III effectors and other candidate virulence genes. Each clade has highly varied complements of accessory genes encoding effectors and toxins with evidence of gain and loss via multiple genetic routes. Genes with orthologs in vascular pathogens were found exclusively within Psa-V. Our analyses capture a pathogen in the early stages of emergence from a predicted source population associated with wild Actinidia species. In addition to candidate genes as targets for resistance breeding programs, our findings highlight the importance of the source population as a reservoir of new disease.


Via Kamoun Lab @ TSL
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Scooped by Ed Rybicki
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World Hepatitis Day Virtual Special Issue - Virology - Elsevier

World Hepatitis Day Virtual Special Issue - Virology - Elsevier | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
World Hepatitis Day, 28 July 2013
This is hepatitis. Know it. Confront it

Every year on 28 July, the World Health Organization and partners...
Ed Rybicki's insight:

Can we have a Papillomavirus day, too?

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Scooped by Chris Kelly
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Cross-reactive human B cell and T cell epitopes between influenza A and B viruses

Influenza A and B viruses form different genera, which were originally distinguished by antigenic differences in their nucleoproteins and matrix 1 proteins.
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Virology Journal | Abstract | West Nile virus methyltransferase domain interacts with protein kinase G

The flaviviral nonstructural protein 5 (NS5) is a phosphoprotein, though the precise identities and roles of many specific phosphorylations remain unknown.
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High-Resolution Temporal Response Patterns to Influenza Vaccine Reveal a Distinct Human Plasma Cell Gene Signature : Nature Publishing Group

High-Resolution Temporal Response Patterns to Influenza Vaccine Reveal a Distinct Human Plasma Cell Gene Signature : Nature Publishing Group | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it

To identify sources of inter-subject variation in vaccine responses, we performed high-frequency sampling of human peripheral blood cells post-vaccination, followed by a novel systems biology analysis. Functional principal component analysis was used to examine time varying B cell vaccine responses. In subjects vaccinated within the previous three years, 90% of transcriptome variation was explained by a single subject-specific mathematical pattern. Within individual vaccine response patterns, a common subset of 742 genes was strongly correlated with migrating plasma cells. Of these, 366 genes were associated with human plasmablasts differentiating in vitro. Additionally, subject-specific temporal transcriptome patterns in peripheral blood mononuclear cells identified migration of myeloid/dendritic cell lineage cells one day after vaccination. Upstream analyses of transcriptome changes suggested both shared and subject-specific transcription groups underlying larger patterns. With robust statistical methods, time-varying response characteristics of individual subjects were effectively captured along with a shared plasma cell gene signature

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Scooped by Chris Upton + helpers
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Check out the #sciconfessions hashtag on twitter for some science fun

e.g.

Once had a metal/ reagent fire in my fume cupboard that had to be put out with liquid N2 due to air/heat sensitivity #sciconfessions

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Ed Rybicki's comment, August 6, 2013 7:18 AM
Once set a labmate on fire with permanganate/benzene mix during a Chemistry prac. Quite spectacular as he ran across the lab, trailing fire...B-)
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A small molecule multi-kinase inhibitor reduces influenza A virus replication by restricting viral RNA synthesis Antiviral Res. 2013

Currently available drugs against influenza virus target the viral neuraminidase or the M2 ion channel. The emergence of viral strains resistant to these drugs has been widely described; therefore, there is an urgent need for novel antiviral drugs. Targeting of host factors required for viral replication is an attractive option for circumventing the problem of drug resistance. Several RNAi screens have demonstrated that host kinases are required for the replication of influenza virus. To determine whether compounds that inhibit these kinases can impair viral replication, we tested several kinase inhibitors for activity against influenza A virus. We demonstrate that the multi-kinase inhibitor ON108110 reduces replication of influenza A virus in a dose-dependent manner by suppressing viral RNA synthesis. In addition, ON108110 also inhibits other viruses including vesicular stomatitis virus and Newcastle disease virus, suggesting that this compound may represent a novel class of antiviral agents.

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Computational analysis of four human adenovirus type 4 genomes reveals molecular evolution through two interspecies recombination events

Computational analysis of four human adenovirus type 4 genomes reveals molecular evolution through two interspecies recombination events | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it

Computational analysis of human adenovirus type 4 (HAdV-E4), a pathogen that is the only HAdV member of species E, provides insights into its zoonotic origin and molecular adaptation. Its genome encodes a domain of the major capsid protein, hexon, from HAdV-B16 recombined into the genome chassis of a simian adenovirus.

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Viral Bioinformatics Resource Center | Viral Bioinformatics Resource Center

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Rescooped by Kenzibit from Host Cell & Pathogen Interactions
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Using Social Media for Scientists Who Swear They Never Would

Using Social Media for Scientists Who Swear They Never Would | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
Dear lab rat,If you found this article on Facebook (or Twitter or Reddit or Google Plus or whatever social media site you prowl), you can stop reading...
Kenzibit's insight:

Worth reading :)

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Ed Rybicki's comment, August 6, 2013 7:20 AM
...sparked a whole lecture (http://www.slideshare.net/edrybicki/why-to-use-social-media) and a series of tweets - thanks, Ken! I wondered how I got to the paper, and it must have been via this post.
Rescooped by Chris Upton + helpers from bioinformatics-databases
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miRandola: The Extracellular / Circulating microRNA Database

miRandola: The Extracellular / Circulating microRNA Database | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it

MicroRNAs (miRNAs) are small (approximately 22 nt) noncoding RNAs that play an important role in the regulation of various biological processes through their interaction with cellular messenger RNAs. They are frequently dysregulated in cancer and have shown promise as tissue-based markers for cancer classification and prognostication. Extracellular miRNAs in serum, plasma, saliva, urine and other body fluids have recently been shown to be associated with various pathological conditions including cancer. miRNAs circulate in the bloodstream in a highly stable, extracellular form, thus they may be used as blood-based biomarkers for cancer and other diseases.

 

Circulating miRNAs are protected by encapsulation in membrane-bound vesicles such as exosomes, but the majority of circulating miRNAs in human plasma and serum cofractionate with Argonaute2 (Ago2) protein, rather than with vesicles. In the present work, we performed a comprehensive classification of different extracellular circulating miRNA types. A direct link to the knowledge base miRò together with the inclusion of datamining facilities allow users to infer possible biological functions of the circulating miRNAs and their connection with the phenotype. To our knowledge miRandola is the first database that provides information about all kind of extracellular miRNAs and we believe that it will constitute a very important resource for researchers.


Via Dr. Stefan Gruenwald
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Rescooped by Chris Upton + helpers from Plant Genomics
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Predicting Network Activity from High Throughput Metabolomics

Predicting Network Activity from High Throughput Metabolomics | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
PLOS Computational Biology is an open-access

Via Biswapriya Biswavas Misra
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Biswapriya Biswavas Misra's curator insight, July 26, 2013 11:25 PM
Abstract

The functional interpretation of high throughput metabolomics by mass spectrometry is hindered by the identification of metabolites, a tedious and challenging task. We present a set of computational algorithms which, by leveraging the collective power of metabolic pathways and networks, predict functional activity directly from spectral feature tables without a priori identification of metabolites. The algorithms were experimentally validated on the activation of innate immune cells.

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Cross-reactive human B cell and T cell epitopes between influenza A and B viruses

Influenza A and B viruses form different genera, which were originally distinguished by antigenic differences in their nucleoproteins and matrix 1 proteins.
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Scooped by Chris Kelly
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svapls: an R package to correct for hidden factors of variability in gene expression studies

Hidden variability is a fundamentally important issue in the context of gene expression studies. Collected tissue samples may have a wide variety of hidden effects that may alter their transcriptional landscape significantly.
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PLOS ONE: Selective Light-Triggered Release of DNA from Gold Nanorods Switches Blood Clotting On and Off

PLOS ONE: Selective Light-Triggered Release of DNA from Gold Nanorods Switches Blood Clotting On and Off | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it

Blood clotting is a precise cascade engineered to form a clot with temporal and spatial control. Current control of blood clotting is achieved predominantly by anticoagulants and thus inherently one-sided. Here we use a pair of nanorods (NRs) to provide a two-way switch for the blood clotting cascade by utilizing their ability to selectively release species on their surface under two different laser excitations. We selectively trigger release of a thrombin binding aptamer from one nanorod, inhibiting blood clotting and resulting in increased clotting time. We then release the complementary DNA as an antidote from the other NR, reversing the effect of the aptamer and restoring blood clotting. Thus, the nanorod pair acts as an on/off switch. One challenge for nanobiotechnology is the bio-nano interface, where coronas of weakly adsorbed proteins can obscure biomolecular function. We exploit these adsorbed proteins to increase aptamer and antidote loading on the nanorods.

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Microbial Informatics and Experimentation: Beginner's guide to comparative bacterial genome analysis using next-generation sequence data

High throughput sequencing is now fast and cheap enough to be considered part of the toolbox for investigating bacteria, and there are thousands of bacterial genome sequences available for comparison in the public domain.
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