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Review: Determinants of virulence of influenza A virus - Online First - Springer

Review: Determinants of virulence of influenza A virus - Online First - Springer | Virology and Bioinformatics from Virology.ca | Scoop.it
Influenza A viruses cause yearly seasonal epidemics and occasional global pandemics in humans. In the last century, four human influenza A virus pandemics have occurred. Occasionally, influenza A viruses that circulate in other species cross the species barrier and infect humans. Virus reassortment (i.e. mixing of gene segments of multiple viruses) and the accumulation of mutations contribute to the emergence of new influenza A virus variants. Fortunately, most of these variants do not have the ability to spread among humans and subsequently cause a pandemic. In this review, we focus on the threat of animal influenza A viruses which have shown the ability to infect humans. In addition, genetic factors which could alter the virulence of influenza A viruses are discussed. The identification and characterisation of these factors may provide insights into genetic traits which change virulence and help us to understand which genetic determinants are of importance for the pandemic potential of animal influenza A viruses.
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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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Integrating alignment-based and alignment-free sequence similarity measures for biological sequence classification

Integrating alignment-based and alignment-free sequence similarity measures for biological sequence classification | Virology and Bioinformatics from Virology.ca | Scoop.it
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Is a small artificial virus fragment the key to a Chikungunya vaccine?

Is a small artificial virus fragment the key to a Chikungunya vaccine? | Virology and Bioinformatics from Virology.ca | Scoop.it
Chikungunya virus (CHIKV) is transmitted by Aedes mosquitoes and causes Chikungunya fever. CHIKV occurs in the tropical and subtropical parts of the world. Regions where it has already caused epide...
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Revision of Begomovirus taxonomy based on pairwise sequence comparisons

Revision of Begomovirus taxonomy based on pairwise sequence comparisons | Virology and Bioinformatics from Virology.ca | Scoop.it

Viruses of the genus Begomovirus (family Geminiviridae) are emergent pathogens of crops throughout the tropical and subtropical regions of the world. By virtue of having a small DNA genome that is easily cloned, and due to the recent innovations in cloning and low-cost sequencing, there has been a dramatic increase in the number of available begomovirus genome sequences. Even so, most of the available sequences have been obtained from cultivated plants and are likely a small and phylogenetically unrepresentative sample of begomovirus diversity, a factor constraining taxonomic decisions such as the establishment of operationally useful species demarcation criteria. In addition, problems in assigning new viruses to established species have highlighted shortcomings in the previously recommended mechanism of species demarcation. Based on the analysis of 3,123 full-length begomovirus genome (or DNA-A component) sequences available in public databases as of December 2012, a set of revised guidelines for the classification and nomenclature of begomoviruses are proposed. The guidelines primarily consider a) genus-level biological characteristics and b) results obtained using a standardized classification tool, Sequence Demarcation Tool, which performs pairwise sequence alignments and identity calculations. These guidelines are consistent with the recently published recommendations for the generaMastrevirus and Curtovirus of the family Geminiviridae. Genome-wide pairwise identities of 91 % and 94 % are proposed as the demarcation threshold for begomoviruses belonging to different species and strains, respectively. Procedures and guidelines are outlined for resolving conflicts that may arise when assigning species and strains to categories wherever the pairwise identity falls on or very near the demarcation threshold value.

 

Ed Rybicki's insight:

Ah, that takes me back: nice all the young ones carry on what we started, back when we invented those generic names!

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Retroviral influence on human embryonic development

Retroviral influence on human embryonic development | Virology and Bioinformatics from Virology.ca | Scoop.it
Some of the thousands of human endogenous retroviral genomes are activated during human embryogenesis, suggesting that they may play a role in development.
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Study of 95,000 children finds no link between MMR vaccines and autism

Study of 95,000 children finds no link between MMR vaccines and autism | Virology and Bioinformatics from Virology.ca | Scoop.it
A study of more than 95,000 children in the US has supported what almost two decades of scientific research has already been telling us - the measles-mumps-rubella vaccine (MMR) is safe and effective and is in no way associated with a heightened...
Hannah Davis's insight:

This study is interesting because they show that even in children with autistic siblings (i.e. kids with a genetic predisposition to autism), vaccination with MMR has no effect on their risk of developing the condition.

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Australian researchers have found a treatment for as-yet incurable hepatitis B

Australian researchers have found a treatment for as-yet incurable hepatitis B | Virology and Bioinformatics from Virology.ca | Scoop.it
A potential cure for hepatitis B virus (HBV) infections has been found by Australian scientists. Australian patients are now the first in the world to have access to the treatment – a combination of an antiviral drug and an anti-cancer drug – which...
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APOBEC3B: Pathological consequences of an innate immune DNA mutator Burns MB, Leonard B, Harris RS - Biomed J

Biomed J, Official publication of Chang Gung University
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Friendly Viruses Protect Us Against Bacteria

Friendly Viruses Protect Us Against Bacteria | Virology and Bioinformatics from Virology.ca | Scoop.it
Viruses in mucus may be important line of defense against disease
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Mutational and fitness landscapes of an RNA virus revealed through population sequencing : Nature

Mutational and fitness landscapes of an RNA virus revealed through population sequencing : Nature | Virology and Bioinformatics from Virology.ca | Scoop.it
RNA viruses exist as genetically diverse populations. It is thought that diversity and genetic structure of viral populations determine the rapid adaptation observed in RNA viruses and hence their pathogenesis. However, our understanding of the mechanisms underlying virus evolution has been limited by the inability to accurately describe the genetic structure of virus populations. Next-generation sequencing technologies generate data of sufficient depth to characterize virus populations, but are limited in their utility because most variants are present at very low frequencies and are thus indistinguishable from next-generation sequencing errors. Here we present an approach that reduces next-generation sequencing errors and allows the description of virus populations with unprecedented accuracy. Using this approach, we define the mutation rates of poliovirus and uncover the mutation landscape of the population. Furthermore, by monitoring changes in variant frequencies on serially passaged populations, we determined fitness values for thousands of mutations across the viral genome. Mapping of these fitness values onto three-dimensional structures of viral proteins offers a powerful approach for exploring structure-function relationships and potentially uncovering new functions. To our knowledge, our study provides the first single-nucleotide fitness landscape of an evolving RNA virus and establishes a general experimental platform for studying the genetic changes underlying the evolution of virus populations.
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A novel codon-optimized SIV gag-pol immunogen for gene-based vaccination

A novel codon-optimized SIV gag-pol immunogen for gene-based vaccination | Virology and Bioinformatics from Virology.ca | Scoop.it

Simian immunodeficiency virus (SIV) is a robust pathogen used in non-human primates to model HIV vaccines. SIV encodes a number of potential vaccine targets. By far the largest and most conserved protein target in SIV is gag-pol encodes many epitopes with potential to drive multivalent T cell responses. While it is an attractive antigen, pol is only translated after a frame shift from gag so that only 1 in 10 gag proteins include this larger antigen. The codon bias of native lentiviral genes are also mismatched with the abundance of tRNAs in mammalian cells resulting in poor expression of unmodified SIV genes. To provide a better SIV gag-pol immunogen for gene-based vaccination, we codon-optimized the full gag-pol sequence from SIVmac239. To increase pol expression, we artificially moved the pol sequence in frame to gag to bypass the need for a translational frame shift for its expression. Finally, we inserted four “self-cleaving” picornavirus sequences into gag p24, protease, reverse transcriptase, and into integrase to fragment the proteins for potentially better immune presentation. We demonstrate that these immunogens are well expressed in vitro and drive similar antibody and T cell responses with or without cleavage sequences.

  
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Adaptive Evolution and Environmental Durability Jointly Structure Phylodynamic Patterns in Avian Influenza Viruses

Adaptive Evolution and Environmental Durability Jointly Structure Phylodynamic Patterns in Avian Influenza Viruses | Virology and Bioinformatics from Virology.ca | Scoop.it
Avian influenza viruses (AIVs) have been pivotal to the origination of human pandemic strains. Despite their scientific and public health significance, however, there remains much to be understood about the ecology and evolution of AIVs in wild birds, where major pools of genetic diversity are generated and maintained. Here, we present comparative phylodynamic analyses of human and AIVs in North America, demonstrating (i) significantly higher standing genetic diversity and (ii) phylogenetic trees with a weaker signature of immune escape in AIVs than in human viruses. To explain these differences, we performed statistical analyses to quantify the relative contribution of several potential explanations. We found that HA genetic diversity in avian viruses is determined by a combination of factors, predominantly subtype-specific differences in host immune selective pressure and the ecology of transmission (in particular, the durability of subtypes in aquatic environments). Extending this analysis using a computational model demonstrated that virus durability may lead to long-term, indirect chains of transmission that, when coupled with a short host lifespan, can generate and maintain the observed high levels of genetic diversity. Further evidence in support of this novel finding was found by demonstrating an association between subtype-specific environmental durability and predicted phylogenetic signatures: genetic diversity, variation in phylogenetic tree branch lengths, and tree height. The conclusion that environmental transmission plays an important role in the evolutionary biology of avian influenza viruses—a manifestation of the “storage effect”—highlights the potentially unpredictable impact of wildlife reservoirs for future human pandemics and the need for improved understanding of the natural ecology of these viruses.
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Data sharing: Make outbreak research open access

Data sharing: Make outbreak research open access | Virology and Bioinformatics from Virology.ca | Scoop.it
Establish principles for rapid and responsible data sharing in epidemics, urge Nathan L. Yozwiak, Stephen F. Schaffner and Pardis C. Sabeti.
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John Oliver calls Dr. Oz "the worst person in scrubs who has ever been on television"

The HBO host encapsulates everything that's wrong with The Dr. Oz Show in one segment.
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BMC Infectious Diseases | Abstract | Medical student’s attitude towards influenza vaccination

Influenza vaccination is recommended for all healthcare personnel (HCP) and most institutions offer vaccination for free and on site. However, medical students do not always have such easy access, and the predictors that might guide the motivation of medical students to get vaccinated are largely unknown.
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The Ebola Epidemic Crystallizes the Potential of Passive Antibody Therapy for Infectious Diseases

The Ebola Epidemic Crystallizes the Potential of Passive Antibody Therapy for Infectious Diseases | Virology and Bioinformatics from Virology.ca | Scoop.it

The current Ebola epidemic provides a dramatic example of the potential of passive antibody therapy for infectious diseases that is also instructive of the hurdles and limitations involved in wide-scale reintroduction of this powerful anti-infective strategy. Passive antibody therapy was first used in the 1890s as "serum therapy" and was the first effective anti-infective therapy. Serum therapy was largely discontinued with the advent of antibiotic therapy in the early 1940s because it could not compete with regards to cost or ease of administration and had additional complexities, including that it had to be administered early in disease, it manifested lot-to-lot variation, and its efficacy required immune donors and the availability of a specific microbiological diagnosis so sera could be matched to the disease-causing microorganism [1]. Serum therapy using heterologous sera was also associated with "serum sickness," a syndrome caused by the formation of antigen-antibody complexes. However, antibiotic therapy was never shown to be superior in efficacy to antibody therapy and there were some conditions, such as pneumococcal pneumonia, where it may have had some advantages. Despite their wholesale abandonment, antibody therapies did retain a niche for certain conditions where no drugs were available, such as the prevention and/or treatment of tetanus, botulism, and certain viral diseases. The development of hybridoma technology and monoclonal antibodies (mAbs) in the mid-1970s promised to solve many of the problems of serum therapy, but, to date, there has not been formal reintroduction of antibody therapies for infectious diseases despite considerable and ongoing efforts to develop such therapies against viral diseases, such as HIV infection, and bacterial diseases, such as those caused byPseudomonas aeruginosa and Staphylacoccous aureus. In contrast, mAbs have revolutionized the treatment of many cancers and rheumatic diseases and dozens have been licensed. Here we analyze why Ab-based therapies remain so underdeveloped for infectious diseases through the prism of the Ebola epidemic.

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Krishan Maggon 's curator insight, April 24, 7:15 AM

Citation: Casadevall A, Pirofski L-a (2015) The Ebola Epidemic Crystallizes the Potential of Passive Antibody Therapy for Infectious Diseases. PLoS Pathog 11(4): e1004717. doi:10.1371/journal.ppat.1004717

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Unprecedented Microbial Diversity Found in Amazonian Tribe | Viruses101 | Learn Science at Scitable

Unprecedented Microbial Diversity Found in Amazonian Tribe | Viruses101 | Learn Science at Scitable | Virology and Bioinformatics from Virology.ca | Scoop.it
In honor of Earth Day, I am diverging from my normal post on viruses to discuss the connection between microbial diversity, antibiotics and industrialization. Not many of us think about the trillions of microbes that live on and inside of us.
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On publishing software

On publishing software | Virology and Bioinformatics from Virology.ca | Scoop.it
This post is a response to Titus and Daniel's blog posts on whether published software should be re-useable, and covers some elements of an argument I had with Aylwyn on Twitter. What is the purpos...
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Florida confirms measles in 2 unvaccinated adults

Florida confirms measles in 2 unvaccinated adults | Virology and Bioinformatics from Virology.ca | Scoop.it
Florida's Department of Health has confirmed two cases of measles in two unvaccinated adults in Indian River County.
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To prevent the next Ebola, scientists try to catch new viruses before they break out

To prevent the next Ebola, scientists try to catch new viruses before they break out | Virology and Bioinformatics from Virology.ca | Scoop.it
With the Ebola outbreak not yet behind us, global health workers are already scrambling to prevent what could be the next big outbreak of an emerging disease caused by a virus that jumped from animals into humans. In Tanzania, an organization is trying a new approach to tracking these new viruses and preventing another pandemic. #
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Near-atomic cryo-EM structure of the helical measles virus nucleocapsid - Science

Measles is a highly contagious human disease. We used cryo-electron microscopy and single particle-based helical image analysis to determine the 4.3 Å resolution structure of the helical nucleocapsid formed by the folded domain of the Measles Virus nucleoprotein encapsidating an RNA. The resulting pseudoatomic model of the Measles Virus nucleocapsid offers important insights into the mechanism of the helical polymerisation of nucleocapsids of negative-strand RNA viruses, in particular via the exchange subdomains of the nucleoprotein.The structure reveals the mode of the nucleoprotein-RNA interaction and explains why each nucleoprotein of Measles Virus binds six nucleotides whereas the Respiratory Syncytial Virus nucleoprotein binds seven. It provides a rational basis for further analysis of Measles Virus replication and transcription, and reveals potential targets for drug design.
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Ebolavirus is evolving but not changing: No evidence for functional change in EBOV from 1976 to the 2014 outbreak. - PubMed - NCBI

The 2014 epidemic of Ebola virus disease (EVD) has had a devastating impact in West Africa. Sequencing of ebolavirus (EBOV) from infected individuals has revealed extensive genetic variation, leading to speculation that the virus may be adapting to humans, accounting for the scale of the 2014 outbreak. We computationally analyze the variation associated with all EVD outbreaks, and find none of the amino acid replacements lead to identifiable functional changes. These changes have minimal effect on protein structure, being neither stabilizing nor destabilizing, are not found in regions of the proteins associated with known functions and tend to cluster in poorly constrained regions of proteins, specifically intrinsically disordered regions. We find no evidence that the difference between the current and previous outbreaks is due to evolutionary changes associated with transmission to humans. Instead, epidemiological factors are likely to be responsible for the unprecedented spread of EVD.

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A review on computational systems biology of pathogen–host interactions | Frontiers | Infectious Diseases

Pathogens manipulate the cellular mechanisms of host organisms via pathogen–host interactions (PHIs) in order to take advantage of the capabilities of host cells, leading to infections. The crucial role of these interspecies molecular interactions in initiating and sustaining infections necessitates a thorough understanding of the corresponding mechanisms. Unlike the traditional approach of considering the host or pathogen separately, a systems-level approach, considering the PHI system as a whole is indispensable to elucidate the mechanisms of infection. Following the technological advances in the post-genomic era, PHI data have been produced in large-scale within the last decade. Systems biology-based methods for the inference and analysis of PHI regulatory, metabolic, and protein–protein networks to shed light on infection mechanisms are gaining increasing demand thanks to the availability of omics data. The knowledge derived from the PHIs may largely contribute to the identification of new and more efficient therapeutics to prevent or cure infections. There are recent efforts for the detailed documentation of these experimentally verified PHI data through Web-based databases. Despite these advances in data archiving, there are still large amounts of PHI data in the biomedical literature yet to be discovered, and novel text mining methods are in development to unearth such hidden data. Here, we review a collection of recent studies on computational systems biology of PHIs with a special focus on the methods for the inference and analysis of PHI networks, covering also the Web-based databases and text-mining efforts to unravel the data hidden in the literature
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SNPer: An R Library for Quantitative Variant Analysis on Single Nucleotide Polymorphisms among Influenza Virus Populations. - PLoS One

Influenza virus (IFV) can evolve rapidly leading to genetic drifts and shifts resulting in human and animal influenza epidemics and pandemics. The genetic shift that gave rise to the 2009 influenza A/H1N1 pandemic originated from a triple gene reassortment of avian, swine and human IFVs. More minor genetic alterations in genetic drift can lead to influenza drug resistance such as the H274Y mutation associated with oseltamivir resistance. Hence, a rapid tool to detect IFV mutations and the potential emergence of new virulent strains can better prepare us for seasonal influenza outbreaks as well as potential pandemics. Furthermore, identification of specific mutations by closely examining single nucleotide polymorphisms (SNPs) in IFV sequences is essential to classify potential genetic markers associated with potentially dangerous IFV phenotypes. In this study, we developed a novel R library called "SNPer" to analyze quantitative variants in SNPs among IFV subpopulations. The computational SNPer program was applied to three different subpopulations of published IFV genomic information. SNPer queried SNPs data and grouped the SNPs into (1) universal SNPs, (2) likely common SNPs, and (3) unique SNPs. SNPer outperformed manual visualization in terms of time and labor. SNPer took only three seconds with no errors in SNP comparison events compared with 40 hours with errors using manual visualization. The SNPer tool can accelerate the capacity to capture new and potentially dangerous IFV strains to mitigate future influenza outbreaks.

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Virology tidbits: Porcine Circovirus: Autophagy. Nucleolus, and Apoptosis

Virology tidbits: Porcine Circovirus: Autophagy. Nucleolus, and Apoptosis | Virology and Bioinformatics from Virology.ca | Scoop.it
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