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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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RegaDB: community-driven data management and analysis for infectious diseases. Bioinformatics. 2013

SUMMARY: RegaDB is a free and open source data management and analysis environment for infectious diseases. RegaDB allows clinicians to store, manage and analyse patient data, including viral genetic sequences. Moreover, RegaDB provides researchers with a mechanism to collect data in a uniform format and offers them a canvas to make newly developed bioinformatics tools available to clinicians and virologists through a user friendly interface.Availability and implementation: Source code, binaries and documentation are available on http://rega.kuleuven.be/cev/regadb. RegaDB is written in the Java programming language, using a web-service-oriented architecture. CONTACT: pieter.libin@rega.kuleuven.be.

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Rising measles outbreaks threaten vaccine-averse

Rising measles outbreaks threaten vaccine-averse | Virology and Bioinformatics from Virology.ca | Scoop.it

Seven confirmed cases of measles in Toronto, Ontario, so far this year, for a total of 12 in Canada to date, are prompting public health officials to remind doctors that the once-common childhood illness risks establishing a foothold again.

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Ed Rybicki's curator insight, May 6, 2013 4:23 PM

And why?  Because risk-averse parents aren't vaccinating their children against the things THEY were vaccinated against, which means we're back in the 1950s again as far as morbidity / mortality figures are concerned.

 

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Inferring duplications, losses, transfers and incomplete lineage sorting with nonbinary species trees

Inferring duplications, losses, transfers and incomplete lineage sorting with nonbinary species trees | Virology and Bioinformatics from Virology.ca | Scoop.it

This is the first reconciliation algorithm to capture all four evolutionary processes driving tree incongruence and the first to reconcile non-binary species trees with a transfer model. Our algorithm infers all optimal solutions and reports complete, temporally feasible event histories, giving the gene and species lineages in which each event occurred.

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A perspective on multiple waves of influenza pandem... [PLoS One. 2013] - PubMed - NCBI

BACKGROUND:

A striking characteristic of the past four influenza pandemic outbreaks in the United States has been the multiple waves of infections. However, the mechanisms responsible for the multiple waves of influenza or other acute infectious diseases are uncertain. Understanding these mechanisms could provide knowledge for health authorities to develop and implement prevention and control strategies.

MATERIALS AND METHODS:

We exhibit five distinct mechanisms, each of which can generate two waves of infections for an acute infectious disease. The first two mechanisms capture changes in virus transmissibility and behavioral changes. The third mechanism involves population heterogeneity (e.g., demography, geography), where each wave spreads through one sub-population. The fourth mechanism is virus mutation which causes delayed susceptibility of individuals. The fifth mechanism is waning immunity. Each mechanism is incorporated into separate mathematical models, and outbreaks are then simulated. We use the models to examine the effects of the initial number of infected individuals (e.g., border control at the beginning of the outbreak) and the timing of and amount of available vaccinations.

RESULTS:

Four models, individually or in any combination, reproduce the two waves of the 2009 H1N1 pandemic in the United States, both qualitatively and quantitatively. One model reproduces the two waves only qualitatively. All models indicate that significantly reducing or delaying the initial numbers of infected individuals would have little impact on the attack rate. Instead, this reduction or delay results in a single wave as opposed to two waves. Furthermore, four of these models also indicate that a vaccination program started earlier than October 2009 (when the H1N1 vaccine was initially distributed) could have eliminated the second wave of infection, while more vaccine available starting in October would not have eliminated the second wave.

  
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A temporal switch model for estimating transcriptional activity in gene expression

A temporal switch model for estimating transcriptional activity in gene expression | Virology and Bioinformatics from Virology.ca | Scoop.it
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Chapter 15: disease gene prioritization. PLoS Comput Biol. 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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Do viruses require the cytoskeleton?

Do viruses require the cytoskeleton? | Virology and Bioinformatics from Virology.ca | Scoop.it
Background

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.

Conclusions

The failure of poisons affecting the cytoskeleton to inhibit the replication of a diverse set of viruses strongly suggests that viruses do not require a functional cytoskeletal system for replication, either because they do not utilize it or are able to utilize alternate pathways when it is not available.

 

Herpesvirus replication graphic from Russell Kightley Media

Ed Rybicki's insight:

Nice review and nice results - rather surprising, too, seeing as I have taught for years that viruses use intracellular transport systems to get around!

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H5N1 Hybrid Viruses Bearing 2009/H1N1 Virus Genes Transmit in Guinea Pigs by Respiratory Droplet

In the past, avian influenza viruses have crossed species’ barriers to trigger human pandemics by reassorting with mammal-infective viruses in intermediate livestock hosts. H5N1 viruses are able to infect pigs, and some of them have affinity for the mammalian type α-2,6-linked sialic acid airway receptor. By using reverse genetics, we systemically created 127 reassortant viruses between a duck isolate of H5N1, specifically retaining its hemagglutinin (HA) gene throughout, and a highly transmissible, human-infective H1N1 virus. We tested the virulence of the reassortants in mice as a correlate for virulence in humans, and tested transmissibility in guinea pigs, which have both avian and mammalian types of airway receptor. Transmission study showed that both polymerase PA gene and nonstructural protein NS gene of H1N1 virus made the H5N1 virus transmissible by respiratory droplet between guinea pigs, without death. Further experiments implicated other H1N1 genes in the enhancement of mammal-to-mammal transmission, including nucleoprotein (NP), neuraminidase (NA), and matrix (M), as well as mutations in H5 HA that improve affinity for human-like airway receptors. Hence, avian H5N1 subtype viruses do have the potential to acquire mammalian transmissibility by reassortment in current agricultural scenarios.

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The TLR4 antagonist Eritoran protects mice from lethal influenza infection

There is a pressing need to develop alternatives to annual influenza vaccines and antiviral agents licensed for mitigating influenza infection. Previous studies reported that acute lung injury caused by chemical or microbial insults is secondary to the generation of host-derived, oxidized phospholipid that potently stimulates Toll-like receptor 4 (TLR4)-dependent inflammation1. Subsequently, we reported that Tlr4−/− mice are highly refractory to influenza-induced lethality2, and proposed that therapeutic antagonism of TLR4 signalling would protect against influenza-induced acute lung injury. Here we report that therapeutic administration of Eritoran (also known as E5564)—a potent, well-tolerated, synthetic TLR4 antagonist3, 4—blocks influenza-induced lethality in mice, as well as lung pathology, clinical symptoms, cytokine and oxidized phospholipid expression, and decreases viral titres. CD14 and TLR2 are also required for Eritoran-mediated protection, and CD14 directly binds Eritoran and inhibits ligand binding to MD2. Thus, Eritoran blockade of TLR signalling represents a novel therapeutic approach for inflammation associated with influenza, and possibly other infections.

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BMC Bioinformatics | Abstract | Quantifying variances in comparative RNA secondary structure prediction

With the advancement of next-generation sequencing and transcriptomics technologies, regulatory effects involving RNA, in particular RNA structural changes are being detected. These results often rely on RNA secondary structure predictions.
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PLOS ONE: A Perspective on Multiple Waves of Influenza Pandemics

PLOS ONE: A Perspective on Multiple Waves of Influenza Pandemics | Virology and Bioinformatics from Virology.ca | Scoop.it
PLOS ONE: an inclusive, peer-reviewed, open-access resource from the PUBLIC LIBRARY OF SCIENCE. Reports of well-performed scientific studies from all disciplines freely available to the whole world.
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BMC Bioinformatics | Full text | The Enzyme Portal: A case study in applying user-centred design methods in bioinformatics

User-centred design (UCD) is a type of user interface design in which the needs and desires of users are taken into account at each stage of the design process for a service or product; often for software applications and websites.
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PLOS ONE: The Genome Sequence of Lone Star Virus, a Highly Divergent Bunyavirus Found in the Amblyomma americanum Tick

Viruses in the family Bunyaviridae infect a wide range of plant, insect, and animal hosts. Tick-borne bunyaviruses in the Phlebovirus genus, including Severe Fever with Thrombocytopenia Syndrome virus (SFTSV) in China, Heartland virus (HRTV) in the United States, and Bhanja virus in Eurasia and Africa have been associated with acute febrile illness in humans. Here we sought to characterize the growth characteristics and genome of Lone Star virus (LSV), an unclassified bunyavirus originally isolated from the lone star tick Amblyomma americanum. LSV was able to infect both human (HeLa) and monkey (Vero) cells. Cytopathic effects were seen within 72 h in both cell lines; vacuolization was observed in infected Vero, but not HeLa, cells. Viral culture supernatants were examined by unbiased deep sequencing and analysis using an in-house developed rapid computational pipeline for viral discovery, which definitively identified LSV as a phlebovirus. De novo assembly of the full genome revealed that LSV is highly divergent, sharing <61% overall amino acid identity with any other bunyavirus. Despite this sequence diversity, LSV was found by phylogenetic analysis to be part of a well-supported clade that includes members of the Bhanja group viruses, which are most closely related to SFSTV/HRTV. The genome sequencing of LSV is a critical first step in developing diagnostic tools to determine the risk of arbovirus transmission by A. americanum, a tick of growing importance given its expanding geographic range and competence as a disease vector. This study also underscores the power of deep sequencing analysis in rapidly identifying and sequencing the genomes of viruses of potential clinical and public health significance.

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High level of susceptibility to human TRIM5alpha conferred by HIV-2 capsid sequences

HIV-2, which was transmitted to humans from a distant primate species (sooty mangabey), differs remarkably from HIV-1 in its infectivity, transmissibility and pathogenicity.
Ed Rybicki's insight:

Finally, some good news about an HIV - OK, it's HIV-2, but still.

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Origin and diversity of novel avian influenza A H7N9 viruses causing human infection: phylogenetic, structural, and coalescent analyses : The Lancet

BackgroundOn March 30, 2013, a novel avian influenza A H7N9 virus that infects human beings was identified. This virus had been detected in six provinces and municipal cities in China as of April 18, 2013. We correlated genomic sequences from avian influenza viruses with ecological information and did phylogenetic and coalescent analyses to extrapolate the potential origins of the virus and possible routes of reassortment events.MethodsWe downloaded H7N9 virus genome sequences from the Global Initiative on Sharing Avian Influenza Data (GISAID) database and public sequences used from the Influenza Virus Resource. We constructed phylogenetic trees and did 1000 bootstrap replicates for each tree. Two rounds of phylogenetic analyses were done. We used at least 100 closely related sequences for each gene to infer the overall topology, removed suspicious sequences from the trees, and focused on the closest clades to the novel H7N9 viruses. We compared our tree topologies with those from a bayesian evolutionary analysis by sampling trees (BEAST) analysis. We used the bayesian Markov chain Monte Carlo method to jointly estimate phylogenies, divergence times, and other evolutionary parameters for all eight gene fragments. We used sequence alignment and homology-modelling methods to study specific mutations regarding phenotypes, specifically addressing the human receptor binding properties.FindingsThe novel avian influenza A H7N9 virus originated from multiple reassortment events. The HA gene might have originated from avian influenza viruses of duck origin, and the NA gene might have transferred from migratory birds infected with avian influenza viruses along the east Asian flyway. The six internal genes of this virus probably originated from two different groups of H9N2 avian influenza viruses, which were isolated from chickens. Detailed analyses also showed that ducks and chickens probably acted as the intermediate hosts leading to the emergence of this virulent H7N9 virus. Genotypic and potential phenotypic differences imply that the isolates causing this outbreak form two separate subclades.InterpretationThe novel avian influenza A H7N9 virus might have evolved from at least four origins. Diversity among isolates implies that the H7N9 virus has evolved into at least two different lineages. Unknown intermediate hosts involved might be implicated, extensive global surveillance is needed, and domestic-poultry-to-person transmission should be closely watched in the future.FundingChina Ministry of Science and Technology Project 973, National Natural Science Foundation of China, China Health and Family Planning Commission, Chinese Academy of Sciences.
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ComplexInsight's curator insight, May 5, 2013 10:37 PM

Firstly sidestepping the important findings for H7N9 virus, this paper illustrates the importance of rgorous methodology and  key research methods for understanding disease evolution and contagence pathways. the paper details  correlated genomic sequences and ecological information using phylogenetic and coalescent analyses to extrapolate the potential originsand  possible routes of reassortment events in H7N9 virus.  As for the findings - novel avian influenza viruses are a major concern for world wide public health - the research work in this paper raises the need for understanding intermediate hosts, viral evolution pathways and domestic poultry wild animation contact on a global scale for future health policy. Worth reading.

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Ebola’s secret weapon revealed

Ebola’s secret weapon revealed, The Newsroom, UTMB
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Ed Rybicki's comment, May 6, 2013 4:40 PM
Yes? And? Abstract!
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Easy Jump for H5N1 from Bird to Mammal

Easy Jump for H5N1 from Bird to Mammal | Virology and Bioinformatics from Virology.ca | Scoop.it
Hybrid viruses derived from an H5N1 bird flu strain can infect guinea pigs through the air.
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Ed Rybicki's curator insight, May 3, 2013 11:14 AM

It is rather concerning that these guys did NOT have to make HA mutations to get their viruses easily transmissible - they just to make reassortants with H5N1 and H1N1pdm viruses.  As could happen in pigs or poultry anywhere both viruses occur....

 
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Chapter 16: text mining for translational bioinformatics [PLoS Comput Biol. 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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Pathogenesis, Transmissibility, and Ocular Tropism of a Highly Pathogenic Avian Influenza A (H7N3) Virus Associated with Human Conjunctivitis

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An Airborne Transmissible Avian Influenza H5 Hemagglutinin Seen at the Atomic Level

Recent studies have identified several mutations in the hemagglutinin (HA) protein that allow the highly pathogenic avian H5N1 influenza A virus to transmit between mammals by airborne route. Here, we determined the complex structures of wild-type and mutant HAs derived from an Indonesia H5N1 virus bound to either avian or human receptor sialic acid analogs. A cis/transconformational change in the glycosidic linkage of the receptor analog was observed, which explains how the H5N1 virus alters its receptor binding preference. Furthermore, the mutant HA possessed low affinities for both avian and human receptors. Our findings provide a structural and biophysical basis for the H5N1 adaptation to acquire human, but maintain avian, receptor binding properties

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Virology Journal | Abstract | The highly pathogenic H7N3 avian influenza strain from July 2012 in Mexico acquired an extended cleavage site through recombination with host 28S rRNA

A characteristic difference between highly and non-highly pathogenic avian influenza strains is the presence of an extended, often multibasic, cleavage motif insertion in the hemagglutinin protein.
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Quest for Edible Malarial Vaccine Leads to Other Potential Medical Uses for Algae

Quest for Edible Malarial Vaccine Leads to Other Potential Medical Uses for Algae | Virology and Bioinformatics from Virology.ca | Scoop.it
Can scientists rid malaria from the Third World by simply feeding algae genetically engineered with a vaccine?
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Ed Rybicki's comment, May 2, 2013 2:31 AM
I commented in Virology News and on my blog, and will do so again here: this is science by press release. The results were modest; the expression levels low - and there is no good evidence to suggest that people could be protected against malaria by eating recombinant Chlamydomonoas.
Ed Rybicki's comment, May 2, 2013 2:32 AM
And because I got cut off...B-) There is enormous potential, however, in plant-made vaccines, and even in using cell-encapsuled proteins to orally vaccinate people. Just not against malaria.
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Guelph Scientists Develop First Vaccine to Help Control Autism-Associated Bacteria | University of Guelph

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The Great Bacterial Bake Off!

If you’re a microbiologist and enjoy baking, then you’re going to love what the Bioscience department (@ICaMB_NCL) at Newcastle University did yesterday. Forget The Great British Bake Off, it’s all about The Great Bacterial Bake Off now!
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