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Sequential Reassortments Underlie Diverse Influenza H7N9 Genotypes in China

Initial genetic characterizations have suggested that the influenza A (H7N9) viruses responsible for the current outbreak in China are novel reassortants. However, little is known about the pathways of their evolution and, in particular, the generation of diverse viral genotypes. Here we report an in-depth evolutionary analysis of whole-genome sequence data of 45 H7N9 and 42 H9N2 viruses isolated from humans, poultry, and wild birds during recent influenza surveillance efforts in China. Our analysis shows that the H7N9 viruses were generated by at least two steps of sequential reassortments involving distinct H9N2 donor viruses in different hosts. The first reassortment likely occurred in wild birds and the second in domestic birds in east China in early 2012. Our study identifies the pathways for the generation of diverse H7N9 genotypes in China and highlights the importance of monitoring multiple sources for effective surveillance of potential influenza outbreaks.

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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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Evolutionary non-linear modelling for selecting vaccines against antigenically variable viruses

Evolutionary non-linear modelling for selecting vaccines against antigenically variable viruses | Virology and Bioinformatics from Virology.ca | Scoop.it
Motivation: In vitro and in vivo selection of vaccines is time consuming, expensive and the selected vaccines may not be able to provide protection against broad-spectrum viruses because of emerging antigenically novel disease strains. A powerful computational model that incorporates these protein/DNA or RNA level fluctuations can effectively predict antigenically variant strains, and can minimize the amount of resources spent on exclusive serological testing of vaccines and make wide spectrum vaccines possible for many diseases. However, in silico vaccine prediction remains a grand challenge. To address the challenge, we investigate the use of linear and non-linear regression models to predict the antigenic similarity in foot-and-mouth disease virus strains and in influenza strains, where the structure and parameters of the non-linear model are optimized using an evolutionary algorithm (EA). In addition, we examine two different scoring methods for weighting the type of amino acid substitutions in the linear and non-linear models. We also test our models with some unseen data.

Results: We achieved the best prediction results on three datasets of SAT2 (Foot-and-Mouth disease), two datasets of serotype A (Foot-and-Mouth disease) and two datasets of influenza when the scoring method based on biochemical properties of amino acids is employed in combination with a non-linear regression model. Models based on substitutions in the antigenic areas performed better than those that took the entire exposed viral capsid proteins. A majority of the non-linear regression models optimized with the EA performed better than the linear and non-linear models whose parameters are estimated using the least-squares method. In addition, for the best models, optimized non-linear regression models consist of more terms than their linear counterparts, implying a non-linear nature of influences of amino acid substitutions. Our models were also tested on five recently generated FMDV datasets and the best model was able to achieve an 80% agreement rate.
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ViRBase: a resource for virus–host ncRNA-associated interactions

ViRBase: a resource for virus–host ncRNA-associated interactions | Virology and Bioinformatics from Virology.ca | Scoop.it

Increasing evidence reveals that diverse non-coding RNAs (ncRNAs) play critically important roles in viral infection. Viruses can use diverse ncRNAs to manipulate both cellular and viral gene expression to establish a host environment conducive to the completion of the viral life cycle. Many host cellular ncRNAs can also directly or indirectly influence viral replication and even target virus genomes. ViRBase (http://www.rna-society.org/virbase) aims to provide the scientific community with a resource for efficient browsing and visualization of virus-host ncRNA-associated interactions and interaction networks in viral infection. The current version of ViRBase documents more than 12 000 viral and cellular ncRNA-associated virus–virus, virus–host, host–virus and host–host interactions involving more than 460 non-redundant ncRNAs and 4400 protein-coding genes from between more than 60 viruses and 20 hosts. Users can query, browse and manipulate these virus–host ncRNA-associated interactions. ViRBase will be of help in uncovering the generic organizing principles of cellular virus–host ncRNA-associated interaction networks in viral infection.

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New Metrics for Evaluating Viral Respiratory Pathogenesis

New Metrics for Evaluating Viral Respiratory Pathogenesis | Virology and Bioinformatics from Virology.ca | Scoop.it
Viral pathogenesis studies in mice have relied on markers of severe systemic disease, rather than clinically relevant measures, to evaluate respiratory virus infection; thus confounding connections to human disease. Here, whole-body plethysmography was used to directly measure changes in pulmonary function during two respiratory viral infections. This methodology closely tracked with traditional pathogenesis metrics, distinguished both virus- and dose-specific responses, and identified long-ter
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Detection of significant protein coevolution

Motivation: The evolution of proteins cannot be fully understood without taking into account the coevolutionary linkages entangling them. From a practical point of view, coevolution between protein families has been used as a way of detecting protein interactions and functional relationships from genomic information. The most common approach to inferring protein coevolution involves the quantification of phylogenetic tree similarity using a family of methodologies termed mirrortree. In spite of their success, a fundamental problem of these approaches is the lack of an adequate statistical framework to assess the significance of a given coevolutionary score (tree similarity). As a consequence, a number of ad hoc filters and arbitrary thresholds are required in an attempt to obtain a final set of confident coevolutionary signals.

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EpiToolKit—a web-based workbench for vaccine design

EpiToolKit is a virtual workbench for immunological questions with a focus on vaccine design. It offers an array of immunoinformatics tools covering MHC genotyping, epitope and neo-epitope prediction, epitope selection for vaccine design, and epitope assembly. In its recently re-implemented version 2.0, EpiToolKit provides a range of new functionality and for the first time allows combining tools into complex workflows. For inexperienced users it offers simplified interfaces to guide the users through the analysis of complex immunological data sets.

 
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The Curious Road from Basic Pathogen Research to Clinical Translation

The Curious Road from Basic Pathogen Research to Clinical Translation | Virology and Bioinformatics from Virology.ca | Scoop.it
The first discovery, made with Alexandra Lucas, revealed that some anti-host viral proteins were powerful inhibitors of the host immune responses to the virus. These viral proteins could be purified individually and used as drugs to inhibit the same immune cells when they become hyper-activated during inflammatory diseases like atherosclerosis. This led to the formation of a new startup biotech company (Viron Therapeutics), and introduced me into the world of applied translational research and clinical trials. Although it is still not a given that viral proteins will end up being approved and licensed for clinical use, I am now an advocate of virus-derived proteins as a new source of drugs to treat immune-based diseases that have no known connection with viruses.

The second discovery, beginning about a decade ago, occurred when we discovered that myxoma virus also grows in many classes of human cancer cells, but not in normal tissues (unless you are a rabbit). In fact, when my longtime collaborator Peter Forsyth injected it into human gliomas transplanted into the brains of test immunodeficient mice, the virus grew selectively within the transplanted human brain tumors just like it does in the internal tissues of myxoma-infected rabbits! Since it is totally nonpathogenic for humans, this discovery has convinced us to develop myxoma virus as a new potential therapeutic for a variety of human cancers. I have now formed a partnership with a biotech company that specializes in virotherapy for cancer (DNAtrix), and our first clinical trial goal will be to improve the outcomes for cancer patients receiving bone marrow transplants. I am very excited about this new approach against cancer in general, but only time will tell whether using live oncolytic viruses to treat cancer will become a licensed clinical tool for oncologists in the future.
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HPV16 Down-Regulates IGFBP2 to Promote Epithelial Invasion in Organotypic Cultures

HPV16 Down-Regulates IGFBP2 to Promote Epithelial Invasion in Organotypic Cultures | Virology and Bioinformatics from Virology.ca | Scoop.it
Author Summary The human papillomaviruses (HPV) are the etiological agents of cervical cancer and the disease progresses through the pre-malignant phases of cervical intraepithelial neoplasia I, II and III (CINI-III), before becoming an invasive carcinoma. Therefore identifying factors, which regulate the transition through the premalignant phases and onto invasive cancer would be of importance clinically, to identify patients at risk of progressing from CIN I to CIN III. We show that express
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Mining the microbial dark matter

Mining the microbial dark matter | Virology and Bioinformatics from Virology.ca | Scoop.it
Microbiologists are finding new ways to explore the vast universe of unknown microbes in the hunt for antibiotics.

Via Cesar Sanchez
Kathleen McLeod's insight:

Look what DNA sequencing can do...

 

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Visualising Geophylogenies in Web Maps Using GeoJSON – PLOS Currents Tree of Life

Visualising Geophylogenies in Web Maps Using GeoJSON – PLOS Currents Tree of Life | Virology and Bioinformatics from Virology.ca | Scoop.it
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Plant virus replication and movement

Plant virus replication and movement | Virology and Bioinformatics from Virology.ca | Scoop.it
Because plant cells are not identical to animal cells, plant viruses are significantly different from animal viruses in several ways.
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HIV-1 and interferons: who's interfering with whom? : Nature Reviews Microbiology : Nature Publishing Group

HIV-1 and interferons: who's interfering with whom? : Nature Reviews Microbiology : Nature Publishing Group | Virology and Bioinformatics from Virology.ca | Scoop.it
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PLOS Computational Biology: Ten Years of PLoS‡ Computational Biology: A Decade of Appreciation and Innovation

PLOS Computational Biology: Ten Years of PLoS‡ Computational Biology: A Decade of Appreciation and Innovation | Virology and Bioinformatics from Virology.ca | Scoop.it
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VirHostNet 2.0: surfing on the web of virus/host molecular interactions data

VirHostNet 2.0: surfing on the web of virus/host molecular interactions data | Virology and Bioinformatics from Virology.ca | Scoop.it

VirHostNet release 2.0 (http://virhostnet.prabi.fr) is a knowledgebase dedicated to the network-based exploration of virus–host protein–protein interactions. Since the previous VirhostNet release (2009), a second run of manual curation was performed to annotate the new torrent of high-throughput protein–protein interactions data from the literature. This resource is shared publicly, in PSI-MI TAB 2.5 format, using a PSICQUIC web service. The new interface of VirHostNet 2.0 is based on Cytoscape web library and provides a user-friendly access to the most complete and accurate resource of virus–virus and virus–host protein–protein interactions as well as their projection onto their corresponding host cell protein interaction networks. We hope that the VirHostNet 2.0 system will facilitate systems biology and gene-centered analysis of infectious diseases and will help to identify new molecular targets for antiviral drugs design. This resource will also continue to help worldwide scientists to improve our knowledge on molecular mechanisms involved in the antiviral response mediated by the cell and in the viral strategies selected by viruses to hijack the host immune system.

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BMC Bioinformatics | Full text | TMFoldRec: a statistical potential-based transmembrane protein fold recognition tool

Transmembrane proteins (TMPs) are the key components of signal transduction, cell-cell adhesion and energy and material transport into and out from the cells. For the deep understanding of these processes, structure determination of transmembrane proteins is indispensable. However, due to technical difficulties, only a few transmembrane protein structures have been determined experimentally. Large-scale genomic sequencing provides increasing amounts of sequence information on the proteins and whole proteomes of living organisms resulting in the challenge of bioinformatics; how the structural information should be gained from a sequence.
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Multi-Dimensional Measurement of Antibody-Mediated Heterosubtypic Immunity to Influenza

Multi-Dimensional Measurement of Antibody-Mediated Heterosubtypic Immunity to Influenza | Virology and Bioinformatics from Virology.ca | Scoop.it
The human immune response to influenza vaccination depends in part on preexisting cross-reactive (heterosubtypic) immunity from previous infection by, and/or vaccination with, influenza strains that share antigenic determinants with the vaccine strains. However, current methods for assessing heterosubtypic antibody responses against influenza, including the hemagglutination-inhibition (HAI) assay and ELISA, are time and labor intensive, and require moderate amounts of serum and reagents. To add
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Unified representation of genetic variants

Summary: A genetic variant can be represented in the Variant Call Format (VCF) in multiple different ways. Inconsistent representation of variants between variant callers and analyses will magnify discrepancies between them and complicate variant filtering and duplicate removal. We present a software tool vt normalize that normalizes representation of genetic variants in the VCF. We formally define variant normalization as the consistent representation of genetic variants in an unambiguous and concise way and derive a simple general algorithm to enforce it. We demonstrate the inconsistent representation of variants across existing sequence analysis tools and show that our tool facilitates integration of diverse variant types and call sets.

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Inter-Seasonal Influenza is Characterized by Extended Virus Transmission and Persistence

Inter-Seasonal Influenza is Characterized by Extended Virus Transmission and Persistence | Virology and Bioinformatics from Virology.ca | Scoop.it
Author Summary Human influenza virus commonly causes disease in the winter months of temperate countries, but exhibits more complex patterns in tropical localities. Most studies of this complex seasonality have only considered viruses sampled within the “normal” influenza season. To help reveal the drivers of influenza seasonality we utilized viruses sampled outside of the normal influenza season, focusing on Australia which is characterized by a wide range of climates. Using a phylogenetic a
Ed Rybicki's insight:

Nice piece of work: helps reinforce the notion that influenza doesn't actually go away, especially in tropical and subtropical areas!

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PLOS Pathogens: Introducing “Research Matters”

PLOS Pathogens: Introducing “Research Matters” | Virology and Bioinformatics from Virology.ca | Scoop.it

In this issue of PLOS Pathogens, we are introducing a new front matter series to allow individual scientists from the many fields that encompass our community of editors, authors, and readers to comment on why the fundamental research in their labs, and that of their collaborators, matters. The genesis of this idea comes from the apparent gulf between working scientists and the general public that seems to be growing ever wider. In particular, there seems to be an expanding gap between what basic researchers and scientists try to accomplish in terms of scientific advancement, and what nonscientists, such as the lay public and the political world, perceive to be accomplished. This diminishes the deliverables expected as a result of funding basic research, the overall value of science to society, and the rational control of scientific funding. We seek this new Research Matters format for individual scientists to “say” in public how diverse fundamental research into pathogens assures real and compelling impact on public health, human knowledge, and life. Our goal is to evolve a forum for active scientists to speak directly, without filters or publicity agents, about why basic research in their field matters. Over time, we hope to develop a collective voice for our community while still preserving the authentic nature of the individual perspective.

 

Ed Rybicki's insight:

Great idea.

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Untangling the origin of viruses and their impact on cellular evolution - 2015 - Annals of the New York Academy of Sciences

Untangling the origin of viruses and their impact on cellular evolution - 2015 - Annals of the New York Academy of Sciences | Virology and Bioinformatics from Virology.ca | Scoop.it
The origin and evolution of viruses remain mysterious. Here, we focus on the distribution of viral replicons in host organisms, their morphological features, and the evolution of highly conserved protein and nucleic acid structures. The apparent inability of RNA viral replicons to infect contemporary akaryotic species suggests an early origin of RNA viruses and their subsequent loss in akaryotes. A census of virion morphotypes reveals that advanced forms were unique to viruses infecting a specific supergroup, while simpler forms were observed in viruses infecting organisms in all forms of cellular life. Results hint toward an ancient origin of viruses from an ancestral virus harboring either filamentous or spherical virions. Finally, phylogenetic trees built from protein domain and tRNA structures in thousands of genomes suggest that viruses evolved via reductive evolution from ancient cells. The analysis presents a complete account of the evolutionary history of cells and viruses and identifies viruses as crucial agents influencing cellular evolution
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TLR3 and TLR9 Agonists Improve Postexposure Vaccination Efficacy of Live Smallpox Vaccines

TLR3 and TLR9 Agonists Improve Postexposure Vaccination Efficacy of Live Smallpox Vaccines | Virology and Bioinformatics from Virology.ca | Scoop.it
Eradication of smallpox and discontinuation of the vaccination campaign resulted in an increase in the percentage of unvaccinated individuals, highlighting the need for postexposure efficient countermeasures in case of accidental or deliberate viral release. Intranasal infection of mice with ectromelia virus (ECTV), a model for human smallpox, is curable by vaccination with a high vaccine dose given up to 3 days postexposure. To further extend this protective window and to reduce morbidity, mic
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The Role of Human Transportation Networks in Mediating the Genetic Structure of Seasonal Influenza in the United States

The Role of Human Transportation Networks in Mediating the Genetic Structure of Seasonal Influenza in the United States | Virology and Bioinformatics from Virology.ca | Scoop.it

The rapid, long-distance spread of human pathogens such as seasonal influenza A across modern transportation networks presents a tremendous challenge for public health. Previous work based on influenza-like illness reports has demonstrated that commuters play an important role in the transmission of influenza across the United States. However, genetic structuring of influenza populations within a single season has not previously been detected. Here, we use sequence data collected over multiple seasons to investigate how human movement along the aviation and commuter networks in the United States contributes to influenza transmission at the regional scale. We confirm that commuters can play an integral role in interstate influenza transmission, but found that this pattern was specific to the influenza A subtype under investigation. 

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How mapping ancestral genes could help the fight against TB

How mapping ancestral genes could help the fight against TB | Virology and Bioinformatics from Virology.ca | Scoop.it
Although one third of the world's population have the TB bacterium, the disease only develops in 10%, which may be linked to genetic factors.
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Broad-spectrum antivirals against viral fusion : Nature Reviews Microbiology : Nature Publishing Group

Broad-spectrum antivirals against viral fusion : Nature Reviews Microbiology : Nature Publishing Group | Virology and Bioinformatics from Virology.ca | Scoop.it
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