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Genomic Variation in Seven Khoe-San Groups Reveals Adaptation and Complex African History

"The history of click-speaking Khoe-San, and African populations in general, remains poorly understood. We genotyped ∼2.3 million SNPs in 220 southern Africans and found that the Khoe-San diverged from other populations ≥100,000 years ago, but structure within the Khoe-San dated back to about 35,000 years ago. Genetic variation in various sub-Saharan populations did not localize the origin of modern humans to a single geographic region within Africa; instead, it indicated a history of admixture and stratification. We found evidence of adaptation targeting muscle function and immune response, potential adaptive introgression of UV-light protection, and selection predating modern human diversification involving skeletal and neurological development. These new findings illustrate the importance of African genomic diversity in understanding human evolutionary history."

 

Ex Africa, semper aliquid novi...or old, in this case!

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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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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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Next-Gen Sequencing Is A Numbers Game | August 18, 2014 Issue - Vol. 92 Issue 33 | Chemical & Engineering News

Next-Gen Sequencing Is A Numbers Game | August 18, 2014 Issue - Vol. 92 Issue 33 | Chemical & Engineering News | Virology and Bioinformatics from Virology.ca | Scoop.it
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VDU's blog: Ebola Virus Disease (EVD) 2014 West African outbreak..

VDU's blog: Ebola Virus Disease (EVD) 2014 West African outbreak.. | Virology and Bioinformatics from Virology.ca | Scoop.it
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40 Greatest Rock Documentaries

40 Greatest Rock Documentaries | Virology and Bioinformatics from Virology.ca | Scoop.it
From meeting the Beatles to Hendrix burning guitars, here are the 40 greatest rock documentaries of all time.
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Just because...

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Ed Rybicki's curator insight, August 20, 10:16 PM

This is one of those "other things" that this site is for B-)

 

Of course, they fail badly by not including "Mad Dogs and Englishmen", but I suppose they got it mostly right.

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The inherent mutational tolerance and antigenic evolvability of influenza hemagglutinin - Elife. 2014

The inherent mutational tolerance and antigenic evolvability of influenza hemagglutinin - Elife. 2014 | Virology and Bioinformatics from Virology.ca | Scoop.it

Influenza is notable for its evolutionary capacity to escape immunity targeting the viral hemagglutinin. We used deep mutational scanning to examine the extent to which a high inherent mutational tolerance contributes to this antigenic evolvability. We created mutant viruses that incorporate most of the ≈104 amino-acid mutations to hemagglutinin from A/WSN/1933 (H1N1) influenza. After passaging these viruses in tissue culture to select for functional variants, we used deep sequencing to quantify mutation frequencies before and after selection. These data enable us to infer the preference for each amino acid at each site in hemagglutinin. These inferences are consistent with existing knowledge about the protein's structure and function, and can be used to create a model that describes hemagglutinin's evolution far better than existing phylogenetic models. We show that hemagglutinin has a high inherent tolerance for mutations at antigenic sites, suggesting that this is one factor contributing to influenza's antigenic evolution.

 

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How a Canadian Prairie city made an Ebola vaccine

How a Canadian Prairie city made an Ebola vaccine | Virology and Bioinformatics from Virology.ca | Scoop.it
An experimental Ebola vaccine that is offering some hope for West Africa was invented in a small Canadian Prairie city and had its roots in the Cold War, the German town of Marburg and a disease scare that panicked Toronto in the 1970s.
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Mutational tolerance helps influenza evade the immune system

Mutational tolerance helps influenza evade the immune system | Virology and Bioinformatics from Virology.ca | Scoop.it
The influenza protein hemagglutinin is highly tolerant of mutations in its antigenic sites, allowing rapid evolution to evade the immune system.
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How Viruses Hijack the ERAD Tuning Machinery

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An essential step during the intracellular life cycle of many positive-strand RNA viruses is the rearrangement of host cell membranes to generate membrane-bound replication platforms. For example, Nidovirales and Flaviviridae subvert the membrane of the endoplasmic reticulum (ER) for their replication. However, the absence of conventional ER and secretory pathway markers in virus-induced ER-derived membranes has for a long time hampered a thorough understanding of their biogenesis.

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Molecular Flipbook: easy way to make videos with structures

Molecular Flipbook: easy way to make videos with structures | Virology and Bioinformatics from Virology.ca | Scoop.it
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A pathogenicity determinant maps to the N-terminal coat protein region of the Pepino mosaic virus genome

A pathogenicity determinant maps to the N-terminal coat protein region of the Pepino mosaic virus genome | Virology and Bioinformatics from Virology.ca | Scoop.it

Pepino mosaic virus poses a worldwide threat to the tomato industry. Considerable differences at the genetic level allow for distinction of four main genotypic clusters, however the basis for phenotypic outcome is difficult to elucidate. This work reports the generation of wild-type PepMV infectious clones of both EU (mild) and CH2 (aggressive) genotypes, from which chimeric infectious clones were created. Phenotypic analysis in three solanaceous hosts; N. benthamiana, D. stramonium and S. lycopersicum, indicated a PepMV pathogenicity determinant to map to the 3’-terminal region of the genome. Increased aggression was only observed in N. benthamiana, showing this factor to be host specific. The determinant was localised to amino acids 11-26 of the N-terminal CP region, this is the first report of this region functioning as virulence factor in PepMV. 

Ed Rybicki's insight:

We're nothing if not current here - even if we DID have to go to the PDF version and copy the abstract, because it's too hot off the press to have an online one yet B-)

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Tailoring Your Proteome View

Tailoring Your Proteome View | Virology and Bioinformatics from Virology.ca | Scoop.it
Computational tools can streamline the development of targeted proteomics experiments.
 
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Nitazoxanide: A first-in-class broad-spectrum antiviral agent

Originally developed and commercialized as an antiprotozoal agent, nitazoxanide was later identified as a first-in-class broad-spectrum antiviral drug and has been repurposed for the treatment of influenza. A Phase 2b/3 clinical trial recently published in The Lancet Infectious Diseases found that oral administration of nitazoxanide 600 mg twice daily for five days reduced the duration of clinical symptoms and reduced viral shedding compared to placebo in persons with laboratory-confirmed influenza. The same study also suggested a potential benefit for subjects with influenza-like illness who did not have influenza or other documented respiratory viral infection. From a chemical perspective, nitazoxanide is the scaffold for a new class of drugs called thiazolides. These small-molecule drugs target host-regulated processes involved in viral replication. Nitazoxanide is orally bioavailable and safe with extensive post-marketing experience involving more than 75 million adults and children. A new dosage formulation of nitazoxanide is presently undergoing global Phase 3 clinical development for the treatment of influenza. Nitazoxanide inhibits a broad range of influenza A and B viruses including influenza A(pH1N1) and the avian A(H7N9) as well as viruses that are resistant to neuraminidase inhibitors. It is synergistic with neuraminidase inhibitors, and combination therapy with oseltamivir is being studied in humans as part of ongoing Phase 3 clinical development. Nitazoxanide also inhibits the replication of a broad range of other RNA and DNA viruses including respiratory syncytial virus, parainfluenza, coronavirus, rotavirus, norovirus, hepatitis B, hepatitis C, dengue, yellow fever, Japanese encephalitis virus and human immunodeficiency virus in cell culture assays. Clinical trials have indicated a potential role for thiazolides in treating rotavirus and norovirus gastroenteritis and chronic hepatitis B and chronic hepatitis C. Ongoing and future clinical development is focused on viral respiratory infections, viral gastroenteritis and emerging infections such as dengue fever.

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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 Protein Discovery Could Clear Path For Treatment - YouTube

Researchers found Ebola's VP24 protein interferes with the body's immune response system. It's a finding that could lead to future treatment. Follow Jay Stru...
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Microbiology: Microbiome science needs a healthy dose of scepticism

Microbiology: Microbiome science needs a healthy dose of scepticism | Virology and Bioinformatics from Virology.ca | Scoop.it
To guard against hype, those interpreting research on the body's microscopic communities should ask five questions, says William P. Hanage.
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Profile Hidden Markov Models for the Detection of Viruses within Metagenomic Sequence Data

Profile Hidden Markov Models for the Detection of Viruses within Metagenomic Sequence Data | 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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Volunteers help British Museum in crowdsourcing archeology project

Volunteers help British Museum in crowdsourcing archeology project | Virology and Bioinformatics from Virology.ca | Scoop.it
Thousands log on to transcribe handwritten catalogue dating back to 18th century and put 30,000 ancient objects online Continue reading...
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WikiWand Makes Wikipedia Beautiful

WikiWand Makes Wikipedia Beautiful | Virology and Bioinformatics from Virology.ca | Scoop.it
Wikipedia is one of the Web’s most visited properties. From quantum mechanics to Laurel and Hardy, the online encyclopedia delivers good primers on just about any topic you can think... Keep reading →
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5 Viruses That Are More Frightening Than Ebola

5 Viruses That Are More Frightening Than Ebola | Virology and Bioinformatics from Virology.ca | Scoop.it

By Elizabeth Palermo, Staff Writer
Published: 08/15/2014 01:58 PM EDT on LiveScience
The Ebola virus has now killed more than 1,000 people in West Africa. Although the mortality rate of the most recent outbreak isn't as high as in previous events, it's still the case that most people who become infected with Ebola will not survive. (The mortality rate is about 60 percent for the current outbreak, compared with 90 percent in the past, according to the National Institutes of Health.)

1. Rabies

2. HIV

3. Influenza

4. Mosquito-borne viruses

5. Rotavirus

 

 
Ed Rybicki's insight:

Amen!  I have a fondness for Ebola simply because it is so spectacularly nasty, but it has killed fewer people in 40 years than flu or rotavirus does in 1.

Seriously: just like charismatic animals like elephants and tigers get all of the headlines when it comes to being endangered, rather than the humble tree frog(s), so do Ebola and Marburg get all of the attention when it comes to reportage on virus epidemics / pandemics.

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Influenza A Virus Attenuation by Codon Deoptimization of the NS Gene for Vaccine Development

Influenza viral infection represents a serious public health problem that causes contagious respiratory disease, which is most effectively prevented through vaccination to reduce transmission and future infection. The nonstructural (NS) gene of influenza A virus encodes an mRNA transcript that is alternatively spliced to express two viral proteins, the nonstructural protein 1 (NS1) and the nuclear export protein (NEP). The importance of the NS gene of influenza A virus for viral replication and virulence has been well described and represents an attractive target to generate live attenuated influenza viruses with vaccine potential.

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The Marine Microbial Eukaryote Transcriptome Sequencing Project (MMETSP): Illuminating the Functional Diversity of Eukaryotic Life in the Oceans through Transcriptome Sequencing

The Marine Microbial Eukaryote Transcriptome Sequencing Project (MMETSP): Illuminating the Functional Diversity of Eukaryotic Life in the Oceans through Transcriptome Sequencing | Virology and Bioinformatics from Virology.ca | Scoop.it
PLOS Biology is an open-access, peer-reviewed journal that features works of exceptional significance in all areas of biological science, from molecules to ecosystems, including works at the interface with other disciplines.
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A Sensitive Tool for Detecting Indels

A Sensitive Tool for Detecting Indels | Virology and Bioinformatics from Virology.ca | Scoop.it

A team from Cold Spring Harbor Laboratory has released an algorithm, called Scalpel, for finding insertions and deletions in next generation sequencing data sets. Scalpel, which is open source and available for download on SourceForge, outperformed the popular tools GATK HaplotypeCaller and SOAPindel in test runs on both simulated and real whole human exomes.

Like other indel callers, Scalpel works by performing de novo assembly of regions of interest, so that misalignment to the reference genome cannot obscure the presence of an insertion or deletion. Scalpel's innovation is to repeatedly check its assembly before comparing to the reference genome, to account for simple sequence repeats that are a regular source of error in indel calling. When Scalpel assembles an exon, it collects reads that map to that exon (including partial matches), splits them into k-mers, and creates a de Bruijn graph to span the exon; however, if it detects repeats in the map, it iteratively increases the size of the k-mers by one base until the repeats are eliminated. This ensures that the final assembly of the exon is highly accurate while minimizing compute time.

 
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AliView: a fast and lightweight alignment viewer and editor for large data sets.

Summary: AliView is an alignment viewer and editor designed to meet the requirements of next generation sequencing era phylogenetic datasets. AliView handles alignments of unlimited size in the formats most commonly used, i.e. Fasta, Phylip, Nexus, Clustal and MSF. The intuitive graphical interface makes it easy to inspect, sort, delete, merge and realign sequences as part of the manual filtering process of large data sets. AliView also works as an easy to use alignment editor for small as well as large data sets.

Availability: AliView is released as open-source software under the GNU General Public License, version 3.0 (GPLv3), and is available at GitHub (www.github.com/AliView). The program is cross-platform and extensively tested on Linux, Mac OS X and Windows systems. Downloads and help are available at http://ormbunkar.se/aliview

Contact: anders.larsson@ebc.uu.se

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Using Clinician's Search Query Data to Monitor Influenza Epidemics

Search query information from a clinician's database, UpToDate, is shown to timely predict influenza epidemics in the United States. Our results show that digital disease surveillance tools based on experts' databases may be able to provide an alternative, reliable and stable signal for accurate predictions of flu outbreaks.

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Quantitative Temporal Viromics: An Approach to Investigate Host-Pathogen Interaction

Quantitative Temporal Viromics: An Approach to Investigate Host-Pathogen Interaction | Virology and Bioinformatics from Virology.ca | Scoop.it

A systematic quantitative analysis of temporal changes in host and viral proteins throughout the course of a productive infection could provide dynamic insights into virus-host interaction. We developed a proteomic technique called “quantitative temporal viromics” (QTV), which employs multiplexed tandem-mass-tag-based mass spectrometry. Human cytomegalovirus (HCMV) is not only an important pathogen but a paradigm of viral immune evasion. QTV detailed how HCMV orchestrates the expression of >8,000 cellular proteins, including 1,200 cell-surface proteins to manipulate signaling pathways and counterintrinsic, innate, and adaptive immune defenses. QTV predicted natural killer and T cell ligands, as well as 29 viral proteins present at the cell surface, potential therapeutic targets. Temporal profiles of >80% of HCMV canonical genes and 14 noncanonical HCMV open reading frames were defined. QTV is a powerful method that can yield important insights into viral infection and is applicable to any virus with a robust in vitro model.

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