Viruses, Immunology & Bioinformatics from Virology.uvic.ca
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Viruses, Immunology & Bioinformatics from Virology.uvic.ca
Virus and bioinformatics articles with some microbiology and immunology thrown in for good measure
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Mutations associated with severity of the pandemic influenza A(H1N1)pdm09 in humans: a systematic review and meta-analysis of epidemiological evidence - Arch Virol. 2014

Abstract

Mutations in the haemagglutinin (HA), non-structural protein 1 (NS1) and polymerase basic protein 2 (PB2) of influenza viruses have been associated with virulence. This study investigated the association between mutations in these genes in influenza A(H1N1)pdm09 virus and the risk of severe or fatal disease. Searches were conducted on the MEDLINE, EMBASE and Web of Science electronic databases and the reference lists of published studies. The PRISMA and STROBE guidelines were followed in assessing the quality of studies and writing-up. Eighteen (18) studies, from all continents, were included in the systematic review (recruiting patients 0 - 77 years old). The mutation D222G was associated with a significant increase in severe disease (pooled RD: 11 %, 95 % CI: 3.0 % - 18.0 %, p = 0.004) and the risk of fatality (RD: 23 %, 95 % CI: 14.0 %-31.0 %, p = < 0.0001). No association was observed between the mutations HA-D222N, D222E, PB2-E627K and NS1-T123V and severe/fatal disease. The results suggest that no virus quasispecies bearing virulence-conferring mutations in the HA, PB2 and NS1 predominated. However issues of sampling bias, and bias due to uncontrolled confounders such as comorbidities, and viral and bacterial coinfection, should be born in mind. Influenza A viruses should continue to be monitored for the occurrence of virulence-conferring mutations in HA, PB2 and NS1. There are suggestions that respiratory virus coinfections also affect virus virulence. Studies investigating the role of genetic mutations on disease outcome should make efforts to also investigate the role of respiratory virus coinfections.

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We'll never find an Ebola vaccine without taking some risks

We'll never find an Ebola vaccine without taking some risks | Viruses, Immunology & Bioinformatics from Virology.uvic.ca | Scoop.it
The current West African ebolavirus outbreak, which has now reached more than 1,000 cases and resulted in more than 800 deaths, is a reminder of the often unpredictable nature of viruses and the difficulties…
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Rewiring of Cellular Membrane Homeostasis by Picornaviruses

Viruses are obligatory intracellular parasites and utilize host elements to support key viral processes, including penetration of the plasma membrane, initiation of infection, replication, and suppression of the host's antiviral defenses. In this review, we focus on picornaviruses, a family of positive-strand RNA viruses, and discuss the mechanisms by which these viruses hijack the cellular machinery to form and operate membranous replication complexes. Studies aimed at revealing factors required for the establishment of viral replication structures identified several cellular-membrane-remodeling proteins and led to the development of models in which the virus used a preexisting cellular-membrane-shaping pathway “as is” for generating its replication organelles. However, as more data accumulate, this view is being increasingly questioned, and it is becoming clearer that viruses may utilize cellular factors in ways that are distinct from the normal functions of these proteins in uninfected cells.

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BLASTing Off – How BLAST Works

BLASTing Off – How BLAST Works | Viruses, Immunology & Bioinformatics from Virology.uvic.ca | Scoop.it
More than a pun on the explosive growth of sequencing data, BLAST makes annotation and comparisons of similar sequences much easier. Created by a group at the U.S. National Center for Biotechnology Information in…
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A Review of “Bioinformatics Algorithms – An Active Learning ...

A Review of “Bioinformatics Algorithms – An Active Learning ... | Viruses, Immunology & Bioinformatics from Virology.uvic.ca | Scoop.it
Each chapter attempts to answer a biological/bioinformatics question, but also has multiple sub-themes for students from different backgrounds. The chapters are so elegantly planned that readers from different backgrounds ...
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Estimating and Predicting Epidemic Behavior for the 2014 West African Ebola Outbreak

Estimating and Predicting Epidemic Behavior for the 2014 West African Ebola Outbreak | Viruses, Immunology & Bioinformatics from Virology.uvic.ca | Scoop.it
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Frontiers | Dendritic cells: Key players in human herpesvirus 8 infection and pathogenesis | Virology

Human herpesvirus 8 (HHV-8; Kaposi’s sarcoma-associated herpesvirus) is an oncogenic gammaherpesvirus that primarily infects cells of the immune and vascular systems. HHV-8 interacts with and targets professional antigen presenting cells (APC) and influences their function. Infection alters the maturation, antigen presentation, and immune activation capabilities of certain dendritic cells (DC) despite non-robust lytic replication in these cells. DC sustain a low level of antiviral functionality during HHV-8 infection in vitro. This may explain the ability of healthy individuals to effectively control this virus without disease. Following an immune compromising event, such as organ transplantation or HIV-1 infection, a reduced cellular antiviral response against HHV-8 compounded with skewed DC cytokine production and antigen presentation likely contributes to the development of HHV-8 associated diseases, i.e., Kaposi’s sarcoma and certain B cell lymphomas. In this review we focus on the role of DC in the establishment of HHV-8 primary and latent infection, the functional state of DC during HHV-8 infection, and the current understanding of the factors influencing virus-DC interactions in the context of HHV-8-associated disease.
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Newest anti-vaxx trend causes babies’ brains to bleed

Newest anti-vaxx trend causes babies’ brains to bleed | Viruses, Immunology & Bioinformatics from Virology.uvic.ca | Scoop.it
Parents are now denying newborns important Vitamin K injections to avoid unnecessary "toxins" VIDEO
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Expansion of Biological Pathways Based on Evolutionary Inference: Cell

Expansion of Biological Pathways Based on Evolutionary Inference: Cell | Viruses, Immunology & Bioinformatics from Virology.uvic.ca | Scoop.it

The availability of diverse genomes makes it possible to predict gene function based on shared evolutionary history. This approach can be challenging, however, for pathways whose components do not exhibit a shared history but rather consist of distinct “evolutionary modules.” We introduce a computational algorithm, clustering by inferred models of evolution (CLIME), which inputs a eukaryotic species tree, homology matrix, and pathway (gene set) of interest. CLIME partitions the gene set into disjoint evolutionary modules, simultaneously learning the number of modules and a tree-based evolutionary history that defines each module. CLIME then expands each module by scanning the genome for new components that likely arose under the inferred evolutionary model. Application of CLIME to ∼1,000 annotated human pathways and to the proteomes of yeast, red algae, and malaria reveals unanticipated evolutionary modularity and coevolving components. CLIME is freely available and should become increasingly powerful with the growing wealth of eukaryotic genomes.

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Ebola treatments caught in limbo

Ebola treatments caught in limbo | Viruses, Immunology & Bioinformatics from Virology.uvic.ca | Scoop.it
Logistics and lack of funds keep experimental drugs and vaccines from being used in Africa outbreak.
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Ebola, Spreading in Africa, Could Land in US

Ebola, Spreading in Africa, Could Land in US | Viruses, Immunology & Bioinformatics from Virology.uvic.ca | Scoop.it
An Ebola outbreak that has killed at least 672 people in Guinea, Liberia and Sierra Leone could land in the U.S., health officials said.
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Analysis of Stop-Gain and Frameshift Variants in Human Innate Immunity Genes

Analysis of Stop-Gain and Frameshift Variants in Human Innate Immunity Genes | Viruses, Immunology & Bioinformatics from Virology.uvic.ca | Scoop.it
PLOS Computational Biology is an open-access (#PLOSCompBio: Analysis of Stop-Gain and Frameshift Variants in Human Innate Immunity Genes http://t.co/nw7bx47t8B)...

Via Gilbert C FAURE
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Coronavirus virulence genes with main focus on SARS-CoV envelope gene

Abstract

Coronavirus (CoV) infection is usually detected by cellular sensors, which trigger the activation of the innate immune system. Nevertheless, CoVs have evolved viral proteins that target different signaling pathways to counteract innate immune responses. Some CoV proteins act as antagonists of interferon (IFN) by inhibiting IFN production or signaling, aspects that are briefly addressed in this review. After CoV infection, potent cytokines relevant in controlling virus infections and priming adaptive immune responses are also generated. However, an uncontrolled induction of these proinflammatory cytokines can lead to pathogenesis and disease severity as described for SARS-CoV and MERS-CoV. The cellular pathways mediated by interferon regulatory factor (IRF)-3 and -7, activating transcription factor (ATF)-2/jun, activator protein (AP)-1, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and nuclear factor of activated T cells (NF-AT), are the main drivers of the inflammatory response triggered after viral infections, with NF-κB pathway the most frequently activated. Key CoV proteins involved in the regulation of these pathways and the proinflammatory immune response are revisited in this manuscript.

It has been shown that the envelope (E) protein plays a variable role in CoV morphogenesis, depending on the CoV genus, being absolutely essential in some cases (genus α CoVs such as TGEV, and genus β CoVs such as MERS-CoV), but not in others (genus β CoVs such as MHV or SARS-CoV). A comprehensive accumulation of data has shown that the relatively small E protein elicits a strong influence on the interaction of SARS-CoV with the host. In fact, after infection with viruses in which this protein has been deleted, increased cellular stress and unfolded protein responses, apoptosis, and augmented host immune responses were observed. In contrast, the presence of E protein activated a pathogenic inflammatory response that may cause death in animal models and in humans.

The modification or deletion of different motifs within E protein, including the transmembrane domain that harbors an ion channel activity, small sequences within the middle region of the carboxy-terminus of E protein, and its most carboxy-terminal end, which contains a PDZ domain-binding motif (PBM), is sufficient to attenuate the virus. Interestingly, a comprehensive collection of SARS-CoVs in which these motifs have been modified elicited full and long-term protection even in old mice, making those deletion mutants promising vaccine candidates. These data indicate that despite its small size, E protein drastically influences the replication of CoVs and their pathogenicity. Although E protein is not essential for CoV genome replication or subgenomic mRNA synthesis, it affects virus morphogenesis, budding, assembly, intracellular trafficking, and virulence. In fact, E protein is responsible in a significant proportion of the inflammasome activation and the associated inflammation elicited by SARS-CoV in the lung parenchyma. This exacerbated inflammation causes edema accumulation leading to acute respiratory distress syndrome (ARDS) and, frequently, to the death of infected animal models or human patients.

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Ebola and ZMapp: What is the 'Secret Serum' That 'Cured' American Doctor Kent Brantly?

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"ZMapp is composed of three 'humanised' monoclonal antibodies manufactured in plants, specifically Nicotiana. It is an optimised cocktail combining the best components of MB-003 and ZMAb.

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Kenzibit's curator insight, August 5, 2014 3:25 PM

"ZMapp is composed of three 'humanised' monoclonal antibodies manufactured in plants, specifically Nicotiana. It is an optimised cocktail combining the best components of MB-003 and ZMAb.

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WebProtégé: a collaborative Web-based platform for editing biomedical ontologies

WebProtégé: a collaborative Web-based platform for editing biomedical ontologies | Viruses, Immunology & Bioinformatics from Virology.uvic.ca | Scoop.it

Summary: WebProtégé is an open-source Web application for editing OWL 2 ontologies. It contains several features to aid collaboration, including support for the discussion of issues, change notification and revision-based change tracking. WebProtégé also features a simple user interface, which is geared towards editing the kinds of class descriptions and annotations that are prevalent throughout biomedical ontologies. Moreover, it is possible to configure the user interface using views that are optimized for editing Open Biomedical Ontology (OBO) class descriptions and metadata. Some of these views are shown in the Supplementary Material and can be seen in WebProtégé itself by configuring the project as an OBO project.

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How lethal is Ebola virus?

How lethal is Ebola virus? | Viruses, Immunology & Bioinformatics from Virology.uvic.ca | Scoop.it
After we discussed newly discovered entry factors for ebolavirus and hepatitis C virus on TWiV 166, the New York Times covered part of the story. (RT @815wrldtrvlr: How lethal is ebolavirus?
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Processing of the Ebola virus glycoprotein by the proprotein convertase furin

Kenzibit's insight:

In the present study, we have investigated processing and maturation of the envelope glycoprotein (GP) of Ebola virus. When GP expressed from vaccinia virus vectors was analyzed by pulse–chase experiments, the mature form and two different precursors were identified. First, the endoplasmic reticulum form preGPer, full-length GP with oligomannosidic N-glycans, was detected. preGPer (110 kDa) was replaced by the Golgi-specific form preGP (160 kDa), full-length GP containing mature carbohydrates. preGP was finally converted by proteolysis into mature GP1,2, which consisted of two disulfide-linked cleavage products, the amino-terminal 140-kDa fragment GP1, and the carboxyl-terminal 26-kDa fragment GP2. GP1,2 was also identified in Ebola virions. Studies employing site-directed mutagenesis revealed that GP was cleaved at a multibasic amino acid motif located at positions 497 to 501 of the ORF. Cleavage was blocked by a peptidyl chloromethylketone containing such a motif. GP is cleaved by the proprotein convertase furin. This was indicated by the observation that cleavage did not occur when GP was expressed in furin-defective LoVo cells but that it was restored in these cells by vector-expressed furin. The Reston subtype, which differs from all other Ebola viruses by its low human pathogenicity, has a reduced cleavability due to a mutation at the cleavage site. As a result of these observations, it should now be considered that proteolytic processing of GP may be an important determinant for the pathogenicity of Ebola virus.

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Kenzibit's curator insight, August 3, 2014 2:50 PM

In the present study, we have investigated processing and maturation of the envelope glycoprotein (GP) of Ebola virus. When GP expressed from vaccinia virus vectors was analyzed by pulse–chase experiments, the mature form and two different precursors were identified. First, the endoplasmic reticulum form preGPer, full-length GP with oligomannosidic N-glycans, was detected. preGPer (110 kDa) was replaced by the Golgi-specific form preGP (160 kDa), full-length GP containing mature carbohydrates. preGP was finally converted by proteolysis into mature GP1,2, which consisted of two disulfide-linked cleavage products, the amino-terminal 140-kDa fragment GP1, and the carboxyl-terminal 26-kDa fragment GP2. GP1,2 was also identified in Ebola virions. Studies employing site-directed mutagenesis revealed that GP was cleaved at a multibasic amino acid motif located at positions 497 to 501 of the ORF. Cleavage was blocked by a peptidyl chloromethylketone containing such a motif. GP is cleaved by the proprotein convertase furin. This was indicated by the observation that cleavage did not occur when GP was expressed in furin-defective LoVo cells but that it was restored in these cells by vector-expressed furin. The Reston subtype, which differs from all other Ebola viruses by its low human pathogenicity, has a reduced cleavability due to a mutation at the cleavage site. As a result of these observations, it should now be considered that proteolytic processing of GP may be an important determinant for the pathogenicity of Ebola virus.

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Structural Differences between the Avian and Human H7N9 Hemagglutinin Proteins Are Attributable to Modifications in Salt Bridge Formation: A Computational Study with Implications in Viral Evolution

Structural Differences between the Avian and Human H7N9 Hemagglutinin Proteins Are Attributable to Modifications in Salt Bridge Formation: A Computational Study with Implications in Viral Evolution | Viruses, Immunology & Bioinformatics from Virology.uvic.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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10 even worse reasons to have a homebirth

10 even worse reasons to have a homebirth | Viruses, Immunology & Bioinformatics from Virology.uvic.ca | Scoop.it
Mommyish just posted a piece entitled 10 Terrible Reasons To Have A Home Birth by Bethany Ramos. It's partly serious and partly tongue in cheek, and accompanied by lots of animated GIFs. Ramos' rea...
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Dr. Kent Brantly reported in ‘grave condition’ as he battles Ebola

Dr. Kent Brantly reported in ‘grave condition’ as he battles Ebola | Viruses, Immunology & Bioinformatics from Virology.uvic.ca | Scoop.it
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New method provides researchers with efficient tool for tagging proteins

New method provides researchers with efficient tool for tagging proteins | Viruses, Immunology & Bioinformatics from Virology.uvic.ca | Scoop.it

Aarhus University researchers have developed an easier method to create DNA–protein conjugates. The method can potentially strengthen the work involved in diagnosing diseases.


Via Integrated DNA Technologies
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Potential 'universal' blood test for cancer discovered

Potential 'universal' blood test for cancer discovered | Viruses, Immunology & Bioinformatics from Virology.uvic.ca | Scoop.it
A simple blood test that can be used to diagnose whether people have cancer or not has been devised by researchers. The test will enable doctors to rule out cancer in patients presenting with certain symptoms, saving time and preventing costly and unnecessary invasive procedures such as colonoscopies and biopsies being carried out. Alternatively, it could be a useful aid for investigating patients who are suspected of having a cancer that is currently hard to diagnose.
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Lecture Slides | HRP214 | Stanford - Writing in the Sciences

Lecture Slides | HRP214 | Stanford - Writing in the Sciences | Viruses, Immunology & Bioinformatics from Virology.uvic.ca | Scoop.it
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Excellent!!!!!

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