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Differential assembly of Hepatitis B Virus core protein on single- and double-stranded nucleic acid suggest the dsDNA-filled core is spring-loaded

Differential assembly of Hepatitis B Virus core protein on single- and double-stranded nucleic acid suggest the dsDNA-filled core is spring-loaded | Virology and Bioinformatics from Virology.ca | Scoop.it

"Hepatitis B Virus (HBV) cores assemble on viral RNA, which is reverse transcribed within the core to the partially dsDNA genome of mature HBV. However, constraining dsDNA, a stiff polymer, within a core necessarily requires far greater capsid stability than constraining ssRNA. We hypothesized that, unlike ssRNA, dsDNA would be a poor substrate for assembly. We examined titrations of ssDNA and dsDNA with purified HBV core protein, Cp183, by EMSA, EM, DLS, and etheno-DNA fluorescence. Cp183 bound ssDNA with high affinity to form virus-like capsids. However, Cp183 bound dsDNA poorly, forming a mixture of irregular complexes. Nonetheless, we observed some normal cores in dsDNA assembly reactions, indicating that the energy required to bend DNA could be similar to the protein–protein association energy. This similarity of energies suggests that dsDNA stresses mature HBV cores, in agreement with calculation, which may be the basis for the virus maturation signal and DNA release."

 

A great paper - and one which harks back to an age where many studies on viruses were biophysical, because the molecular biological techniques we use now had simply not been invented.  I note frequent reference to Bancroft, 1970 - to a paper on self-assembly of plant viruses.  I also like the concept of HBV cores as a Jack-in-a-box: ready to pop open to deliver the goodies.

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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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It's a group effort - the curators:

It's a group effort - the curators: | Virology and Bioinformatics from Virology.ca | Scoop.it

get in touch if you want to help curate this topic

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Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak

In its largest outbreak, Ebola virus disease is spreading through Guinea, Liberia, Sierra Leone, and Nigeria. We sequenced 99 Ebola virus genomes from 78 patients in Sierra Leone to ~2,000x coverage. We observed a rapid accumulation of interhost and intrahost genetic variation, allowing us to characterize patterns of viral transmission over the initial weeks of the epidemic. This West African variant likely diverged from Middle African lineages ~2004, crossed from Guinea to Sierra Leone in May 2014, and has exhibited sustained human-to-human transmission subsequently, with no evidence of additional zoonotic sources. Since many of the mutations alter protein sequences and other biologically meaningful targets, they should be monitored for impact on diagnostics, vaccines, and therapies critical to outbreak response.

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Scientists found the origins of the Ebola outbreak — by tracking its mutations

Scientists found the origins of the Ebola outbreak — by tracking its mutations | Virology and Bioinformatics from Virology.ca | Scoop.it
Genetic sequences of dozens of Ebola virus samples will provide much needed information for fighting the disease.
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Top 5 bash commands for handling data – Code, Think, Write

Top 5 bash commands for handling data – Code, Think, Write | Virology and Bioinformatics from Virology.ca | Scoop.it
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Scientific method: Statistical errors

Scientific method: Statistical errors | Virology and Bioinformatics from Virology.ca | Scoop.it
P values, the 'gold standard' of statistical validity, are not as reliable as many scientists assume.
Chris Upton + helpers's insight:

Worth repeating...

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Datavu: Useful Unix commands for exploring data

Datavu: Useful Unix commands for exploring data | Virology and Bioinformatics from Virology.ca | Scoop.it
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The EMPRES-i genetic module: a novel tool linking epidemiological outbreak information and genetic characteristics of influenza viruses

Combining epidemiological information, genetic characterization and geomapping in the analysis of influenza can contribute to a better understanding and description of influenza epidemiology and ecology, including possible virus reassortment events. Furthermore, integration of information such as agroecological farming system characteristics can provide new knowledge on risk factors of influenza emergence and spread. Integrating viral characteristics into an animal disease information system is therefore expected to provide a unique tool to trace-and-track particular virus strains; generate clade distributions and spatiotemporal clusters; screen for distribution of viruses with specific molecular markers; identify potential risk factors; and analyze or map viral characteristics related to vaccines used for control and/or prevention. For this purpose, a genetic module was developed within EMPRES-i (FAO’s global animal disease information system) linking epidemiological information from influenza events with virus characteristics and enabling combined analysis. An algorithm was developed to act as the interface between EMPRES-i disease event data and publicly available influenza virus sequences in OpenfluDB. This algorithm automatically computes potential links between outbreak event and sequences, which are subsequently manually validated by experts. Subsequently, other virus characteristics such as antiviral resistance can then be associated to outbreak data. To visualize such characteristics on a geographic map, shape files with virus characteristics to overlay on other EMPRES-i map layers (e.g. animal densities) can be generated. The genetic module allows export of associated epidemiological and sequence data for further analysis. FAO has made this tool available for scientists and policy makers. Contributions are expected from users to improve and validate the number of linked influenza events and isolate information as well as the quality of information. Possibilities to interconnect with other influenza sequence databases or to expand the genetic module to other viral diseases (e.g. foot and mouth disease) are being explored.

Database OpenfluDB URL: http://openflu.vital-it.ch

Database EMPRES-i URL: http://EMPRES-i.fao.org/

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Engineered plant virus resistance

Abstract

Virus diseases are among the key limiting factors that cause significant yield loss and continuously threaten crop production. Resistant cultivars coupled with pesticide application are commonly used to circumvent these threats. One of the limitations of the reliance on resistant cultivars is the inevitable breakdown of resistance due to the multitude of variable virus populations. Similarly, chemical applications to control virus transmitting insect vectors are costly to the farmers, cause adverse health and environmental consequences, and often result in the emergence of resistant vector strains. Thus, exploiting strategies that provide durable and broad-spectrum resistance over diverse environments are of paramount importance.

The development of plant gene transfer systems has allowed for the introgression of alien genes into plant genomes for novel disease control strategies, thus providing a mechanism for broadening the genetic resources available to plant breeders. Genetic engineering offers various options for introducing transgenic virus resistance into crop plants to provide a wide range of resistance to viral pathogens. This review examines the current strategies of developing virus resistant transgenic plants.

KeywordsBroad-spectrum resistance;Transgenic plants;Plant viruses;Gene silencing;Agrobacterium;Plant biotechnology


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Rabenstein, Frank's comment, August 28, 8:44 AM
Chris Upton and helpers, thank you rescooping
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Microbial response to Deepwater Horizon oil spill

The ISME Journal: Multidisciplinary Journal of Microbial Ecology is the official Journal of the International Society for Microbial Ecology, publishing high-quality, original research papers, short communications, commentary articles and reviews in the rapidly expanding and diverse discipline of microbial ecology.
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Coordinated Evolution of Influenza A Surface Proteins

Coordinated Evolution of Influenza A Surface Proteins | Virology and Bioinformatics from Virology.ca | Scoop.it

Surface proteins hemagglutinin (HA) and neuraminidase (NA) of the human influenza A virus evolve under selection pressure to escape the human adaptive immune response and antiviral drug treatments. In addition to these external selection pressures, some mutations in HA are known to affect the adaptive landscape of NA, and vice versa, because these two proteins are physiologically interlinked. However, the extent to which evolution of one protein affects the evolution of the other is unknown. Here we develop a novel phylogenetic method for detecting the signatures of such genetic interactions between mutations in different genes, that is, inter-gene epistasis. Using this method, we show that influenza surface proteins evolve in a coordinated way, with substitutions in HA affecting substitutions in NA and vice versa, at many sites. Of particular interest is our finding that the oseltamivir-resistance mutations in NA in subtype H1N1 were likely facilitated by prior mutations in HA. Our results illustrate that the adaptive landscape of a viral protein is remarkably sensitive to its genomic context and, more generally, imply that the evolution of any single protein must be understood within the context of the entire evolving genome.

 
Ed Rybicki's insight:

Cool stuff - and so is the fact that they used BioRxiv, the "Preprint Server for Biology".  Some day, most biological papers may be done like this...B-)

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The 3 Dumbest Things About Whole Foods Market

The 3 Dumbest Things About Whole Foods Market | Virology and Bioinformatics from Virology.ca | Scoop.it
Whole Foods Market sells wonderful fresh food, but they also sell homeopathic remedies and nutritional supplements, promoting them with little more than hand-waving claims about "immune support." For real medicine, go somewhere else.
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Progress in the Prevention and Treatment of RSV Infection — NEJM

At long last, gratifying progress is evident on many fronts in combating respiratory syncytial virus (RSV) infection. RSV was discovered in 1956 as an agent causing coryza in chimpanzees.1 Its clinical effects became evident shortly thereafter through a strong epidemiologic association of RSV infection with bronchiolitis and pneumonia in young infants.2 In the almost 60 years since the virus was identified, the highlights of RSV research have been relatively few, in spite of dedicated groups working in this field. The reasons for this include the difficulty of working with RSV in the laboratory; the confinement of RSV replication in humans . . .

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Influenza A and B Virus Intertypic Reassortment through Compatible Viral Packaging Signals

Influenza A and B Virus Intertypic Reassortment through Compatible Viral Packaging Signals | Virology and Bioinformatics from Virology.ca | Scoop.it

Influenza A and B viruses cocirculate in humans and together cause disease and seasonal epidemics. These two types of influenza viruses are evolutionarily divergent, and exchange of genetic segments inside coinfected cells occurs frequently within types but never between influenza A and B viruses. Possible mechanisms inhibiting the intertypic reassortment of genetic segments could be due to incompatible protein functions of segment homologs, a lack of processing of heterotypic segments by influenza virus RNA-dependent RNA polymerase, an inhibitory effect of viral proteins on heterotypic virus function, or an inability to specifically incorporate heterotypic segments into budding virions. Here, we demonstrate that the full-length hemagglutinin (HA) of prototype influenza B viruses can complement the function of multiple influenza A viruses. We show that viral noncoding regions were sufficient to drive gene expression for either type A or B influenza virus with its cognate or heterotypic polymerase. The native influenza B virus HA segment could not be incorporated into influenza A virus virions. However, by adding the influenza A virus packaging signals to full-length influenza B virus glycoproteins, we rescued influenza A viruses that possessed HA, NA, or both HA and NA of influenza B virus. Furthermore, we show that, similar to single-cycle infectious influenza A virus, influenza B virus cannot incorporate heterotypic transgenes due to packaging signal incompatibilities. Altogether, these results demonstrate that the lack of influenza A and B virus reassortants can be attributed at least in part to incompatibilities in the virus-specific packaging signals required for effective segment incorporation into nascent virions.

 

Flu virus mixing graphic from Russell Kightley Media

 

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Ebola Outbreak Strains Sequenced | The Scientist Magazine®

Ebola Outbreak Strains Sequenced | The Scientist Magazine® | Virology and Bioinformatics from Virology.ca | Scoop.it
Ninety-nine publicly available genomes could help researchers working to develop diagnostics, vaccines, and therapies. 
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Seals May Have Carried Tuberculosis To The New World – Phenomena: Not Exactly Rocket Science

Seals May Have Carried Tuberculosis To The New World – Phenomena: Not Exactly Rocket Science | Virology and Bioinformatics from Virology.ca | Scoop.it
Very few people suspected the seals. Kirsten Bos from the University of Tubingen certainly didn’t when she and her colleagues started studying three Peruvian skeletons. They were just trying to und...
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Genomes reveal start of Ebola outbreak

Jung Choi's insight:

An invaluable resource that cost the lives of 5 of the authors of the paper.

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Microbial impacts on insect evolutionary diversification: from patterns to mechanisms

Microbial impacts on insect evolutionary diversification: from patterns to mechanisms | Virology and Bioinformatics from Virology.ca | Scoop.it
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Immuno-PCR: molecular and Immunological techniques combined in DNA amplification

Immuno-PCR: molecular and Immunological techniques combined in DNA amplification | Virology and Bioinformatics from Virology.ca | Scoop.it
Introduction Since the first immunoassays were developed in the 1950's the variety of assay formats has increased dramatically.

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Alfredo Corell's curator insight, September 22, 2013 2:29 PM

This new method, termed immuno-polymerase chain reaction (immuno-PCR), benefits from the specificity of antibodies and the sensitivity of PCR. Several independent studies undertaken since the publication of this seminal paper have consistently demonstrated the advantages of this technique over traditional ELISA, some achieving more than a 50,000 fold increase in sensitivity over the equivalent immunoassay [2]. Furthermore, immuno-PCR can be used in a multiplex format and offers accurate quantitation.

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Tobacco-derived 'plantibodies' enter the fight against Ebola

Tobacco-derived 'plantibodies' enter the fight against Ebola | Virology and Bioinformatics from Virology.ca | Scoop.it
NEW YORK (Reuters) - Drugmakers' use of the tobacco plant as a fast and cheap way to produce novel biotechnology treatments is gaining global attention because of its role in an experimental Ebola therapy.The

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Ed Rybicki's curator insight, August 27, 2:20 AM

Nice account of ZMapp and some of the science behind it.

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Lecturer/Senior Lecturer (Level B/C) in Bioinformatics

Lecturer/Senior Lecturer (Level B/C) in Bioinformatics | Virology and Bioinformatics from Virology.ca | Scoop.it
Lecturer/Senior Lecturer (Level B/C) in Synthetic Biology, Research Fellow (Level B) in Synthetic Biology & Lecturer/Senior Lecturer (Level B/C) in Bioinformatics Apply now Job no: 494553 Work type: Continuing full time Vacancy type: External...

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[2013.12.02] Mads Albertsen: Extracting Genomes from Metagenomes

Invited lecture at University of Vienna on extracting genomes from metagenomes.

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Viruses might tame some algal blooms | Science News

Viruses might tame some algal blooms | Science News | Virology and Bioinformatics from Virology.ca | Scoop.it
The rapid demise of a giant, carbon-spewing algal bloom points to the influence of viral wranglers.
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BMC Bioinformatics | Full text | ReformAlign: improved multiple sequence alignments using a profile-based meta-alignment approach

Obtaining an accurate sequence alignment is fundamental for consistently analyzing biological data. Although this problem may be efficiently solved when only two sequences are considered, the exact inference of the optimal alignment easily gets computationally intractable for the multiple sequence alignment case. To cope with the high computational expenses, approximate heuristic methods have been proposed that address the problem indirectly by progressively aligning the sequences in pairs according to their relatedness. These methods however are not flexible to change the alignment of an already aligned group of sequences in the view of new data, resulting thus in compromises on the quality of the deriving alignment. In this paper we present ReformAlign, a novel meta-alignment approach that may significantly improve on the quality of the deriving alignments from popular aligners. We call ReformAlign a meta-aligner as it requires an initial alignment, for which a variety of alignment programs can be used. The main idea behind ReformAlign is quite straightforward: at first, an existing alignment is used to construct a standard profile which summarizes the initial alignment and then all sequences are individually re-aligned against the formed profile. From each sequence-profile comparison, the alignment of each sequence against the profile is recorded and the final alignment is indirectly inferred by merging all the individual sub-alignments into a unified set. The employment of ReformAlign may often result in alignments which are significantly more accurate than the starting alignments.
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▶ Webinar: BLAST in the Cloud - YouTube

Presented July 30, 2014 and covering: an NCBI BLAST AMI at Amazon Web Services; introduction to AWS and setting up an instance; running command line BLAST an...
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Shotgun glycomics of pig lung identifies natural endogenous receptors for influenza viruses

Shotgun glycomics of pig lung identifies natural endogenous receptors for influenza viruses | Virology and Bioinformatics from Virology.ca | Scoop.it
Significance

Studies using novel “shotgun glycan microarray” technology identify, for the first time to our knowledge, the endogenous receptors for influenza viruses from a natural host, the pig. Libraries of total N-glycans from pig lung were probed for binding properties using a panel of influenza viruses isolated from humans, birds, and swine. Natural glycan receptors were identified for all viruses examined, and although some displayed the rather broad α2,3 or α2,6 sialic acid linkage specificity conventionally associated with avian or human viruses, other strains were highly specific, revealing a complexity that has not been demonstrated previously. Because pigs are often implicated as intermediate hosts for pandemic viruses, these results and the approaches described will transform our understanding of influenza host range, transmission, and pathogenicity.

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Live attenuated influenza vaccine strains elicit a greater innate immune response than antigenically-matched seasonal influenza viruses

Live attenuated influenza vaccine strains elicit a greater innate immune response than antigenically-matched seasonal influenza viruses | Virology and Bioinformatics from Virology.ca | Scoop.it

Influenza viruses are global pathogens that infect approximately 10-20% of the world's population each year. Vaccines, including the live attenuated influenza vaccine (LAIV), are the best defense against influenza infections. The LAIV is a novel vaccine that actively replicates in the human nasal epithelium and elicits both mucosal and systemic protective immune responses. The differences in replication and innate immune responses following infection of human nasal epithelium with influenza seasonal wild type (WT) and LAIV viruses remain unknown. Using a model of primary differentiated human nasal epithelial cell (hNECs) cultures, we compared influenza WT and antigenically-matched cold adapted (CA) LAIV virus replication and the subsequent innate immune response including host cellular pattern recognition protein expression, host innate immune gene expression, secreted pro-inflammatory cytokine production, and intracellular viral RNA levels. Growth curves comparing virus replication between WT and LAIV strains revealed significantly less infectious virus production during LAIV compared with WT infection. Despite this disparity in infectious virus production the LAIV strains elicited a more robust innate immune response with increased expression of RIG-I, TLR-3, IFNβ, STAT-1, IRF-7, MxA, and IP-10. There were no differences in cytotoxicity between hNEC cultures infected with WT and LAIV strains as measured by basolateral levels of LDH. Elevated levels of intracellular viral RNA during LAIV as compared with WT virus infection of hNEC cultures at 33°C may explain the augmented innate immune response via the up-regulation of pattern recognition receptors and down-stream type I IFN expression. Taken together our results suggest that the decreased replication of LAIV strains in human nasal epithelial cells is associated with a robust innate immune response that differs from infection with seasonal influenza viruses, limits LAIV shedding and plays a role in the silent clinical phenotype seen in human LAIV inoculation.

 

Ed Rybicki's insight:

Well, of course they do: they engage ALL the levers making the immune system work!

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