Virology and Bioinformatics from Virology.ca
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Virology and Bioinformatics from Virology.ca
Virus and bioinformatics articles with some microbiology and immunology thrown in for good measure
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World Immunisation Week: The fight against TB

This week is ‘World Immunisation Week’, which aims to promote vaccinations, particularly amongst the 22 million infants which are not protected with routine immunisations.
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PLOS Genetics: Genetic and Genomic Architecture of the Evolution of Resistance to Antifungal Drug Combinations

PLOS Genetics: Genetic and Genomic Architecture of the Evolution of Resistance to Antifungal Drug Combinations | Virology and Bioinformatics from Virology.ca | Scoop.it

Here, we evolved experimental populations of the model yeast Saccharomyces cerevisiae and the leading human fungal pathogen Candida albicans with azole and an inhibitor of Hsp90, geldanamycin, or calcineurin, FK506. To recapitulate a clinical context where Hsp90 or calcineurin inhibitors could be utilized in combination with azoles to render resistant pathogens responsive to treatment, the evolution experiment was initiated with strains that are resistant to azoles in a manner that depends on Hsp90 and calcineurin. Of the 290 lineages initiated, most went extinct, yet 14 evolved resistance to the drug combination. Drug target mutations that conferred resistance to geldanamycin or FK506 were identified and validated in five evolved lineages.

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PLOS Pathogens: A Mechanistic Paradigm for Broad-Spectrum Antivirals that Target Virus-Cell Fusion

PLOS Pathogens: A Mechanistic Paradigm for Broad-Spectrum Antivirals that Target Virus-Cell Fusion | Virology and Bioinformatics from Virology.ca | Scoop.it
From molecules to physiology
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PLOS Pathogens: Immune Regulation during Helminth Infections

PLOS Pathogens: Immune Regulation during Helminth Infections | Virology and Bioinformatics from Virology.ca | Scoop.it

Helminth is a nonphylogenetic term that refers to multicellular animals (or metazoans) that have adopted a parasitic lifestyle in mammalian hosts. They are more commonly referred to as parasitic worms. These worms generally (with the exception of Strongyloides stercoralis) cannot replicate within the host, and they have evolved distinct methods to co-exist with their host through the activation of an immune regulatory network.

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Global Assessment of Resistance to Neuraminidase Inhibitors, 2008–2011: The Influenza Resistance Information Study (IRIS)

Background. Following emergence of naturally occurring oseltamivir-resistant influenza A(H1N1) viruses, a global observational investigation, the Influenza Resistance Information Study (IRIS; NCT00884117), was initiated in 2008 to study neuraminidase inhibitor (NAI) resistance and clinical outcome.

Methods. Patients with influenza-like illness and/or positive rapid test results agreed to swabs of the posterior nares that were assessed by semiquantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) for influenza type and subtype and NAI resistance. RT-qPCR–positive specimens were cultured, sequenced, and phenotypically tested for NAI resistance. Treatment was at the physician's discretion.

Results. Of 1799 influenza-positive (RT-qPCR) patients, 1281 had influenza A (47 seasonal H1N1; 335 H3N2; 899 H1N1pdm2009) and 518 had influenza B. Antivirals were administered to 1041 (58%) patients (26, 245, 514, and 256, respectively). All seasonal H1N1 strains were genotypically (H275Y) and phenotypically resistant to oseltamivir. No genotypic resistance was detected in the day 1 samples of any other viral subtypes. Mutation-specific (MS) RT-PCR detected resistance to oseltamivir in 19 patients postbaseline (17 H1N1pdm2009 [H275Y]; 2 H3N2 [R292K]), 14 of whom were children aged ≤5 years. In 12 of 19 patients, viral loads were too low to permit cell culture and 14 of 19 were RT-qPCR negative by day 10. In 1 other H1N1pdm2009 patient, H275Y was detected by sequencing but not by MS RT-PCR. No emergent resistance was found in influenza B infections.

Conclusions. In years 1–3 of IRIS, emergent resistance to oseltamivir in influenza viruses during treatment was uncommon (2.2%) and mostly found in patients aged 1–5 years. Viral loads were low in many cases and viral clearance rapid.

 
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Reflections on the early development of poxvirus vec... [Vaccine. 2013] - PubMed - NCBI

Poxvirus expression vectors were described in 1982 and quickly became widely used for vaccine development as well as research in numerous fields. Advantages of the vectors include simple construction, ability to accommodate large amounts of foreign DNA and high expression levels. Numerous poxvirus-based veterinary vaccines are currently in use and many others are in human clinical trials. The early reports of poxvirus vectors paved the way for and stimulated the development of other viral vectors and recombinant DNA vaccines.

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Broadly neutralizing antibodies against influenza virus [Antiviral Res. 2013]

Despite available antivirals and vaccines, influenza continues to be a major cause of mortality worldwide. Vaccination generally induces an effective, but strain-specific antibody response. As the virus continually evolves, new vaccines have to be administered almost annually when a novel strain becomes dominant. Furthermore, the sporadic emerging resistance to neuraminidase inhibitors among circulating strains suggests an urgent need for new therapeutic agents. 

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PLOS Pathogens: Pandemic Influenza A Viruses Escape from Restriction by Human MxA through Adaptive Mutations in the Nucleoprotein

PLOS Pathogens: Pandemic Influenza A Viruses Escape from Restriction by Human MxA through Adaptive Mutations in the Nucleoprotein | Virology and Bioinformatics from Virology.ca | Scoop.it
From molecules to physiology
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Increased CD8+ T Cell Response to Epstein-Barr Virus Lytic Antigens in the Active Phase of Multiple Sclerosis

Increased CD8+ T Cell Response to Epstein-Barr Virus Lytic Antigens in the Active Phase of Multiple Sclerosis | Virology and Bioinformatics from Virology.ca | Scoop.it
From molecules to physiology
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The B cell response and hemagglutinin stalk-reactive antibody production in different age cohorts following 2009 H1N1 influenza vaccination [Clin Vaccine Immunol. 2013]

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.
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MicroMicrobe • Microbial image of the month I’ve previously...

MicroMicrobe • Microbial image of the month I’ve previously... | Virology and Bioinformatics from Virology.ca | Scoop.it
Microbial image of the month


I’ve previously posted an image of a single phage, but this month’s image shows phages in action, infecting a bacterial cell.
Naomi Osborne's insight:

Fab image of phages in action

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A really gentle introduction to Hidden Markov Models. : MachineLearning

A really gentle introduction to Hidden Markov Models. : MachineLearning | Virology and Bioinformatics from Virology.ca | Scoop.it
reddit: the front page of the internet

several links to resources, books and examples...

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PLOS Pathogens: A Mechanistic Paradigm for Broad-Spectrum Antivirals that Target Virus-Cell Fusion

LJ001 is a lipophilic thiazolidine derivative that inhibits the entry of numerous enveloped viruses at non-cytotoxic concentrations (IC50≤0.5 µM), and was posited to exploit the physiological difference between static viral membranes and biogenic cellular membranes. We now report on the molecular mechanism that results in LJ001's specific inhibition of virus-cell fusion.

The antiviral activity of LJ001 was light-dependent, required the presence of molecular oxygen, and was reversed by singlet oxygen (1O2) quenchers, qualifying LJ001 as a type II photosensitizer. Unsaturated phospholipids were the main target modified by LJ001-generated1O2. Hydroxylated fatty acid species were detected in model and viral membranes treated with LJ001, but not its inactive molecular analog, LJ025. 1O2-mediated allylic hydroxylation of unsaturated phospholipids leads to a trans-isomerization of the double bond and concurrent formation of a hydroxyl group in the middle of the hydrophobic lipid bilayer. LJ001-induced 1O2-mediated lipid oxidation negatively impacts on the biophysical properties of viral membranes (membrane curvature and fluidity) critical for productive virus-cell membrane fusion. LJ001 did not mediate any apparent damage on biogenic cellular membranes, likely due to multiple endogenous cytoprotection mechanisms against phospholipid hydroperoxides.

Based on our understanding of LJ001's mechanism of action, we designed a new class of membrane-intercalating photosensitizers to overcome LJ001's limitations for use as an in vivoantiviral agent. Structure activity relationship (SAR) studies led to a novel class of compounds (oxazolidine-2,4-dithiones) with (1) 100-fold improved in vitro potency (IC50<10 nM), (2) red-shifted absorption spectra (for better tissue penetration), (3) increased quantum yield (efficiency of 1O2 generation), and (4) 10–100-fold improved bioavailability. Candidate compounds in our new series moderately but significantly (p≤0.01) delayed the time to death in a murine lethal challenge model of Rift Valley Fever Virus (RVFV). The viral membrane may be a viable target for broad-spectrum antivirals that target virus-cell fusion.

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Dengue Viral Fusion

Dengue was created for Irene Bosch, Ph.D. at University of Massachusetts and Yorgo Modis, Ph.D. from Yale University. This animation was an educational proje...
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Vaccinia and influenza A viruses select rathe than adjust tRNAs to optimize translation

Transfer RNAs (tRNAs) are central to protein synthesis and impact translational speed and fidelity by their abundance. Here we examine the extent to which viruses manipulate tRNA populations to favor translation of their own genes. We study two very different viruses: influenza A virus (IAV), a medium-sized (13 kB genome) RNA virus; and vaccinia virus (VV), a large (200 kB genome) DNA virus. We show that the total cellular tRNA population remains unchanged following viral infection, whereas the polysome-associated tRNA population changes dramatically in a virus-specific manner. The changes in polysome-associated tRNA levels reflect the codon usage of viral genes, suggesting the existence of local tRNA pools optimized for viral translation.

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Virology Journal | Abstract | Do viruses require the cytoskeleton?

It is generally thought that viruses require the cytoskeleton during their replication cycle. However, recent experiments in our laboratory with rubella virus, a member of the family Togaviridae (genus rubivirus), revealed that replication proceeded in the presence of drugs that inhibit microtubules. This study was done to expand on this observation. Findings The replication of three diverse viruses, Sindbis virus (SINV; family Togaviridae family), vesicular stomatitis virus (VSV; family Rhabdoviridae), and Herpes simplex virus (family Herpesviridae), was quantified by the titer (plaque forming units/ml; pfu/ml) produced in cells treated with one of three anti-microtubule drugs (colchicine, noscapine, or paclitaxel) or the anti-actin filament drug, cytochalasin D. None of these drugs affected the replication these viruses. Specific steps in the SINV infection cycle were examined during drug treatment to determine if alterations in specific steps in the virus replication cycle in the absence of a functional cytoskeletal system could be detected, i.e. redistribution of viral proteins and replication complexes or increases/decreases in their abundance. These investigations revealed that the observable impacts were a colchicine-mediated fragmentation of the Golgi apparatus and concomitant intracellular redistribution of the virion structural proteins, along with a reduction in viral genome and sub-genome RNA levels, but not double-stranded RNA or protein levels.

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Why does smallpox vaccine shield some, not others? It's in the genes, study finds

Why does smallpox vaccine shield some, not others? It's in the genes, study finds | Virology and Bioinformatics from Virology.ca | Scoop.it
How well people are protected by the smallpox vaccine depends on more than the quality of the vaccination: individual genes can alter their response, Mayo Clinic research shows.
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ScienceDirect.com - Trends in Microbiology - Fleas and smaller fleas: virotherapy for parasite infections

Bacteriophages are viruses of bacteria that are used for controlling bacterial food-borne pathogens and have been proposed for more extensive usage in infection control. Protists are now recognised to harbour viruses and virus-like particles. We propose that investigation of their prevalence in parasites be intensified. We also propose that such viruses might be considered for virotherapy to control certain parasite infections of man and animals.

  
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HIV Plays (and Wins) a Game of T Cell Brinkmanship

HIV Plays (and Wins) a Game of T Cell Brinkmanship | Virology and Bioinformatics from Virology.ca | Scoop.it
PLOS Biology is an open-access, peer-reviewed journal that features works of exceptional significance in all areas of biological science, from molecules to ecosystems, including works at the interface with other disciplines.
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BMC Biology |Biological functions of natural antisense #transcripts

In theory, the human genome is large enough to keep its roughly 20,000 genes well separated. In practice, genes are clustered; even more puzzling, in many cases both DNA strands of a protein coding gene are transcribed.
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BMC Bioinformatics | Base calling for high-throughput short-read sequencing: dynamic programming solutions

Background Next-generation DNA sequencing platforms are capable of generating millions of reads in a matter of days at rapidly reducing costs.
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Prokaryote-expressed M2e protein improves H9N2 influenza vaccine efficacy and protection against lethal influenza a virus in mice

Influenza vaccines are prepared annually based on global epidemiological surveillance data.
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Cowpox virus employs a two-pronged strategy to outflank MHCI antigen presentation.

Smallpox decimated humanity for thousands of years before being eradicated by vaccination, a success facilitated by the fact that humans are the only host of variola virus. In contrast, other orthopoxviruses such as cowpox virus can infect a variety of mammalian species, although its dominant reservoir appears to be rodents. This difference in host specificity suggests that cowpox may have developed promiscuous immune evasion strategies to facilitate zoonosis. Recent experiments have established that cowpox can disrupt MHCI antigen presentation during viral infection of both human and murine cells, a process enabled by two unique proteins, CPXV012 and CPXV203. While CPXV012 inhibits antigenic peptide transport from the cytosol to the ER, CPXV203 blocks MHCI trafficking to the cell surface by exploiting the KDEL-receptor recycling pathway. Our recent investigations of CPXV203 reveal that it binds a diverse array of classical and non-classical MHCI proteins with dramatically increased affinities at the lower pH of the Golgi relative to the ER, thereby providing mechanistic insight into how it works synergistically with KDEL receptors to block MHCI surface expression. The strategy used by cowpox to both limit peptide supply and disrupt trafficking of fully assembled MHCI acts as a dual-edged sword that effectively disables adaptive immune surveillance of infected cells.

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PLOS Genetics: Plant-Symbiotic Fungi as Chemical Engineers: Multi-Genome Analysis of the Clavicipitaceae Reveals Dynamics of Alkaloid Loci

PLOS Genetics: Plant-Symbiotic Fungi as Chemical Engineers: Multi-Genome Analysis of the Clavicipitaceae Reveals Dynamics of Alkaloid Loci | Virology and Bioinformatics from Virology.ca | Scoop.it

Results indicated a strong tendency for alkaloid loci to have conserved cores that specify the skeleton structures and peripheral genes that determine chemical variations that are known to affect their pharmacological specificities. Generally, gene locations in cluster peripheries positioned them near to transposon-derived, AT-rich repeat blocks, which were probably involved in gene losses, duplications, and neofunctionalizations. The alkaloid loci in the epichloae had unusual structures riddled with large, complex, and dynamic repeat blocks. This feature was not reflective of overall differences in repeat contents in the genomes, nor was it characteristic of most other specialized metabolism loci.

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