Viruses and Bioinformatics from Virology.uvic.ca
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Viruses and Bioinformatics from Virology.uvic.ca
Virus and bioinformatics articles with some microbiology and immunology thrown in for good measure
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Genome-wide analysis of influenza viral RNA and nucleoprotein association | Nucleic Acids Research | Oxford Academic

Genome-wide analysis of influenza viral RNA and nucleoprotein association | Nucleic Acids Research | Oxford Academic | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
Influenza A virus (IAV) genomes are composed of eight single-stranded RNA segments that are coated by viral nucleoprotein (NP) molecules. Classically, the interaction between NP and viral RNA (vRNA) is depicted as a uniform pattern of ‘beads on a string’. Using high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (HITS-CLIP), we identified the vRNA binding profiles of NP for two H1N1 IAV strains in virions. Contrary to the prevailing model for vRNA packaging, NP does not bind vRNA uniformly in the A/WSN/1933 and A/California/07/2009 strains, but instead each vRNA segment exhibits a unique binding profile, containing sites that are enriched or poor in NP association. Intriguingly, both H1N1 strains have similar yet distinct NP binding profiles despite extensive sequence conservation. Peaks identified by HITS-CLIP were verified as true NP binding sites based on insensitivity to DNA antisense oligonucleotide-mediated RNase H digestion. Moreover, nucleotide content analysis of NP peaks revealed that these sites are relatively G-rich and U-poor compared to the genome-wide nucleotide content, indicating an as-yet unidentified sequence bias for NP association in vivo. Taken together, our genome-wide study of NP–vRNA interaction has implications for the understanding of influenza vRNA architecture and genome packaging.
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The Institute for the Study of Non–Model Organisms and other fantasies


While there are many reasons for our collective reluctance to pursue these orphaned genetic elements, lack of funding probably ranks at the top of the list.

Thus there is a great need for an institute devoted entirely to the study of uncharacterized genes. SWAT-like teams of investigators at the institute would be tasked with rapidly characterizing these genes. A battery of reagents, including antibodies, green fluorescent protein constructs, mutants, RNAi and CRISPR constructs, and purified proteins, would be developed for this work. Once every year, the results of their efforts would be published in PLoS Neglected Genes.

In the entrance hall of this well-funded institute would be a Rube Goldberg exhibit, the kind you see at airports, consisting of ramps, tubes, levels, pulleys, paddles, and springs that transport ping-pong balls. Once a year, on April 14th (the declared date of completion of sequencing the human genome), all 365 researchers would gather around the exhibit for the “Selection Ceremony.” Each would grab a ball as it bounces off a small trampoline. These balls would have the gene identification numbers of 365 randomly selected, uncharacterized genes. The researchers’ task is clear: they have a year to characterize their assigned genes.

Cindy's insight:
A fun and exciting read!
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DNA sequencing and big data open a new frontier in the hunt for new viruses

DNA sequencing and big data open a new frontier in the hunt for new viruses | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
Cross-species jumps may play unexpectedly big role in virus evolution
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Environmental drivers of viral community composition in Antarctic soils identified by viromics

Environmental drivers of viral community composition in Antarctic soils identified by viromics | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
The Antarctic continent is considered the coldest and driest place on earth with simple ecosystems, devoid of higher plants. Soils in the ice-free regions of Antarctica are known to harbor a wide range of microorganisms from primary producers to grazers, yet their ecology and particularly the role of viruses is poorly understood. In this study, we examined the virus community structures of 14 soil samples from the Mackay Glacier region. Viral communities were extracted from soil and the dsDNA was extracted, amplified using single-primer amplification, and sequenced using the Ion Torrent Proton platform. Metadata on soil physico-chemistry was collected from all sites. Both read and contig datasets were analyzed with reference-independent and reference-dependent methods to assess viral community structures and the influence of environmental parameters on their distribution. We observed a high heterogeneity in virus signatures, independent of geographical proximity. Tailed bacteriophages were dominant in all samples, but the incidences of the affiliated families Siphoviridae and Myoviridae were inversely correlated, suggesting direct competition for hosts. Viruses of the families Phycodnaviridae and Mimiviridae were present at significant levels in high-diversity soil samples and were found to co-occur, implying little competition between them. Combinations of soil factors, including pH, calcium content, and site altitude, were found to be the main drivers of viral community structure. The pattern of viral community structure with higher levels of diversity at lower altitude and pH, and co-occurring viral families, suggests that these cold desert soil viruses interact with each other, the host, and the environment in an intricate manner, playing a potentially crucial role in maintaining host diversity and functioning of the microbial ecosystem in the extreme environments of Antarctic soil.
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A cross-species view on viruses. - PubMed - NCBI

Curr Opin Virol. 2012 Oct;2(5):561-8. doi: 10.1016/j.coviro.2012.07.003. Epub 2012 Jul 24. Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Review
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Salk scientists solve longstanding biological mystery of DNA organization - Salk Institute for Biological Studies

Salk scientists solve longstanding biological mystery of DNA organization - Salk Institute for Biological Studies | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
Clodagh
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A virus with a green thumb

A virus with a green thumb | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
I just love it when long standing mysteries in virology are suddenly solved, typically by the use of new technologies. In this story, the long standing mystery was why poxvirus mRNAs have a stretch of poly(A) in their 5′-noncoding regions. The answer is that it allows the ribosome to preferentially translate these viral mRNAs over those of the host
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Scientists challenge next-generation sequencing dogma: Surprising bacteria study reveals that shotgun sequencing misses major groups of organisms despite producing more data than amplicon sequencing

Scientists challenge next-generation sequencing dogma: Surprising bacteria study reveals that shotgun sequencing misses major groups of organisms despite producing more data than amplicon sequencing | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
Next-generation sequencing -- the ability to sequence millions or billions of small fragments of DNA in parallel -- has revolutionized the biological sciences, playing an essential role in everything from locating mutations that cause human disease to determining how a newly discovered animal fits into the tree of life. But a new study reveals that a favored sequencing method for measuring microbial biodiversity is not as accurate as once thought.
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Dengue subgenomic RNA disrupts immunity in mosquito salivary glands to increase virus transmission

Dengue subgenomic RNA disrupts immunity in mosquito salivary glands to increase virus transmission | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
Author summary Dengue is a re-emerging global disease transmitted from human-to-human by mosquitoes. While environmental and host immune factors are important, viral determinants of mosquito transmission also shape the epidemiology of dengue. Understanding how dengue viruses influence transmission will help identify isolates with high epidemic potential and untangle the evolutionary pressures at play in the dual-host cycle. Here, we identified 2 substitutions in the 3’UTR of epidemic isolates that increase transmission through immune suppression in the salivary glands. Using oral infection of Aedes aegypti mosquitoes, we reported that epidemic isolates produced more subgenomic flaviviral RNA (sfRNA) in salivary glands. SfRNA is generated from the 3’UTR sequence remaining after partial genome degradation by a host nuclease. Using reverse genetics, we identified the two 3’UTR substitutions responsible for the higher sfRNA quantity in salivary glands. We further showed that these substitutions increased dengue virus titer in salivary glands and rate of saliva infection, and suppressed the Toll immune response in salivary glands. Our study identifies the substitutions that determine virus epidemiological fitness and provides a mechanism for sfRNA-mediated enhancement of transmission. Together with previous work demonstrating that sfRNA sequence modification influences dengue virus pathogenicity in human, and that shows variation in sfRNA sequence when the viruses transition from one host to vector and vice versa, our study supports that sfRNA evolution is constrained in the two hosts.
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The tetraspanin CD9 facilitates MERS-coronavirus entry 

The tetraspanin CD9 facilitates MERS-coronavirus entry  | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
Author summary Enveloped viruses rank among the most dangerous zoonotically emerging pathogens. Their cell entry often requires multiple transmembrane proteins in the target cell, which may interact with each other to promote viral-cell membrane fusion. Susceptibility to virus infection may correlate with these transmembrane protein interactions. Here we report that the scaffolding tetraspanin protein CD9 links the receptor for MERS-CoV to a membrane fusion-activating protease called TMPRSS2, forming a complex that promotes rapid and efficient infection. The related human CoV strain 229E was also facilitated by CD9, indicating that multiple CoVs depend on tetraspanin-directed clustering of receptors and proteases for efficient cell entry. Reliance on CD9 specifically applied to virulent, in vivo mouse lung-adapted MERS-CoVs, suggesting that the most efficient virus entry pathways in natural respiratory CoV infections are facilitated by tetraspanins. This suggestion was reinforced by selectively regulating gene expression in vivo, using recombinant adenovirus transducing vectors. The findings demonstrated that CD9 facilitated MERS-CoV infections in mice.
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Decoding the Geometry of Viruses Could Lead to Better Vaccines

Decoding the Geometry of Viruses Could Lead to Better Vaccines | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
Mathematical insights into how RNA helps viruses pull together their protein shells could guide future studies of viral behavior and function.
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Identical Protein Groups: Non-redundant access to protein records

Identical Protein Groups: Non-redundant access to protein records | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
  Have you ever searched the NCBI Protein database and been overwhelmed with the number of sequences returned? Have you tried searching with a protein name, thinking that would greatly limit the results, only to still be presented with many sequences (all with the same name)? It’s a common problem in this time of greatly…
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Latency, Integration, and Reactivation of Human Herpesvirus-6

Human herpesvirus-6A (HHV-6A) and human herpesvirus-6B (HHV-6B) are two closely related viruses that infect T-cells. Both HHV-6A and HHV-6B possess telomere-like repeats at the terminal regions of their genomes that facilitate latency by integration into the host telomeres, rather than by episome formation. In about 1% of the human population, human herpes virus-6 (HHV-6) integration into germline cells allows the viral genome to be passed down from one generation to the other; this condition is called inherited chromosomally integrated HHV-6 (iciHHV-6). This review will cover the history of HHV-6 and recent works that define the biological differences between HHV-6A and HHV-6B. Additionally, HHV-6 integration and inheritance, the capacity for reactivation and superinfection of iciHHV-6 individuals with a second strain of HHV-6, and the role of hypomethylation of human chromosomes during integration are discussed. Overall, the data suggest that integration of HHV-6 in telomeres represent a unique mechanism of viral latency and offers a novel tool to study not only HHV-6 pathogenesis, but also telomere biology. Paradoxically, the integrated viral genome is often defective especially as seen in iciHHV-6 harboring individuals. Finally, gaps in the field of HHV-6 research are presented and future studies are proposed.
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Preventive effect of human papillomavirus vaccination on the development of uterine cervical lesions in young Japanese women. - PubMed - NCBI

Preventive effect of human papillomavirus vaccination on the development of uterine cervical lesions in young Japanese women. - PubMed - NCBI | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
J Obstet Gynaecol Res. 2017 Jul 14. doi: 10.1111/jog.13419. [Epub ahead of print]
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Cross-species jumps may play unexpectedly big role in virus evolution

Cross-species jumps may play unexpectedly big role in virus evolution | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
On occasion, a virus may jump from one host species to another and adapt to the new host. Such cross-species transmission happens more often than expected, according to new research published in PLOS Pathogens, and it ma
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Study opens new drug therapy targets in a range of diseases

“This study shows for the first time that signalling happens downstream of ‘toll-like receptors’ – proteins that play a key role in the innate immune system,” Professor Kobe said. “These receptors are a double-edged sword. “On one hand, they protect us against infection, but they are also responsible for pathological inflammatory responses in a range of disorders from chronic inflammatory, autoimmune, cardiovascular and cancer-related disorders to pathologies associated with infections.” “For this reason, the associated pathways are important drug targets for a range of diseases.”
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An auditory display tool for DNA sequence analysis

An auditory display tool for DNA sequence analysis | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
DNA Sonification refers to the use of an auditory display to convey the information content of DNA sequence data. Six sonification algorithms are presented that each produce an auditory display. These algorithms are logically designed from the simple through to the more complex. Three of these parse individual nucleotides, nucleotide pairs or codons into musical notes to give rise to 4, 16 or 64 notes, respectively. Codons may also be parsed degenerately into 20 notes with respect to the genetic code. Lastly nucleotide pairs can be parsed as two separate frames or codons can be parsed as three reading frames giving rise to multiple streams of audio. The most informative sonification algorithm reads the DNA sequence as codons in three reading frames to produce three concurrent streams of audio in an auditory display. This approach is advantageous since start and stop codons in either frame have a direct affect to start or stop the audio in that frame, leaving the other frames unaffected. Using these methods, DNA sequences such as open reading frames or repetitive DNA sequences can be distinguished from one another. These sonification tools are available through a webpage interface in which an input DNA sequence can be processed in real time to produce an auditory display playable directly within the browser. The potential of this approach as an analytical tool is discussed with reference to auditory displays derived from test sequences including simple nucleotide sequences, repetitive DNA sequences and coding or non-coding genes. This study presents a proof-of-concept that some properties of a DNA sequence can be identified through sonification alone and argues for their inclusion within the toolkit of DNA sequence browsers as an adjunct to existing visual and analytical tools.
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University says prominent Japanese cell biologist committed misconduct

University says prominent Japanese cell biologist committed misconduct | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
University of Tokyo investigated anonymous allegations of manipulated images in papers by Yoshinori Watanabe.
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Cells that stand in the way of HIV cure: Discovery expands understanding of marrow's role

Cells that stand in the way of HIV cure: Discovery expands understanding of marrow's role | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
Every day, 17 million HIV-infected people around the world swallow pills that keep the virus inside them at bay.

Via Gilbert C FAURE
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Engineering resistance to virus transmission

Engineering plants for resistance to virus transmission by invertebrate vectors has lagged behind other forms of plant protection. Vectors typically transmit more than one virus. Thus, vector resistance could provide a wider range of protection than defenses directed solely against one virus or virus group. We discuss current knowledge of vector–host–virus interactions, the roles of viral gene products in host and vector manipulation, and the effects of semiochemicals on host–vector interactions, and how this knowledge could be employed to disrupt transmission dynamics. We also discuss how resistance to vectors could be generated through genetic engineering or gene editing or indirectly through use of biocontrol using plant-resident viruses that infect vectors.
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Discovery Could Help Predict the Next Influenza Pandemic

Discovery Could Help Predict the Next Influenza Pandemic | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
Every year we go through the same motions: Scientists figure out what the most common flu strains will be, and prepare a vaccine that will best protect against it. Those who get vaccinated avoid the new strains, those who don’t might get sick. But every so often, a new kind of flu pops up that doctors are unprepared to vaccinate against. That kind of flu can turn into a pandemic.
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Protection of tombusviral double-stranded RNA replication intermediate against reconstituted RNAi

Protection of tombusviral double-stranded RNA replication intermediate against reconstituted RNAi | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
Author summary Positive-strand RNA viruses build membranous replication compartment to support their replication in the infected hosts. One of the proposed functions of the usurped subcellular membranes is to protect the viral RNA from recognition and destruction by various cellular RNA sensors and ribonucleases. To answer this fundamental question on the putative role of co-opted host factors and membranes in protecting the viral double-stranded RNA replication intermediate during replication, the authors took advantage of yeast (Saccharomyces cerevisiae), which lacks the conserved RNAi machinery, as a surrogate host for TBSV. The reconstituted RNAi machinery from S. castellii in S. cerevisiae was used as an intracellular probe to study the effect of various co-opted cellular proteins and lipids on the formation of RNAi-insensitive replication compartment. Overall, the authors demonstrate the interaction between the RNAi machinery and the viral replicase complex, and the essential roles of usurped host factors in protecting the viral dsRNA replication intermediate from RNAi-based degradation.
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IcyTree: rapid browser-based visualization for phylogenetic trees and networks | Bioinformatics | Oxford Academic

IcyTree: rapid browser-based visualization for phylogenetic trees and networks | Bioinformatics | Oxford Academic | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
Summary: IcyTree is an easy-to-use application which can be used to visualize a wide variety of phylogenetic trees and networks. While numerous phylogenetic tree viewers exist already, IcyTree distinguishes itself by being a purely online tool, having a responsive user interface, supporting phylogenetic networks (ancestral recombination graphs in particular), and efficiently drawing trees that include information such as ancestral locations or trait values. IcyTree also provides intuitive panning and zooming utilities that make exploring large phylogenetic trees of many thousands of taxa feasible.Availability and Implementation: IcyTree is a web application and can be accessed directly at http://tgvaughan.github.com/icytree. Currently supported web browsers include Mozilla Firefox and Google Chrome. IcyTree is written entirely in client-side JavaScript (no plugin required) and, once loaded, does not require network access to run. IcyTree is free software, and the source code is made available at http://github.com/tgvaughan/icytree under version 3 of the GNU General Public License.Contact:tgvaughan@gmail.com
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Big names in statistics want to shake up much-maligned P value

Big names in statistics want to shake up much-maligned P value | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
One of scientists’ favourite statistics — the P value — should face tougher standards, say leading researchers.
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Bioinformatics: indispensable, yet hidden in plain sight?

Bioinformatics: indispensable, yet hidden in plain sight? | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
Bioinformatics has multitudinous identities, organisational alignments and disciplinary links. This variety allows bioinformaticians and bioinformatic work to contribute to much (if not most) of life science research in profound ways. The multitude of bioinformatic work also translates into a multitude of credit-distribution arrangements, apparently dismissing that work. We report on the epistemic and social arrangements that characterise the relationship between bioinformatics and life science. We describe, in sociological terms, the character, power and future of bioinformatic work. The character of bioinformatic work is such that its cultural, institutional and technical structures allow for it to be black-boxed easily. The result is that bioinformatic expertise and contributions travel easily and quickly, yet remain largely uncredited. The power of bioinformatic work is shaped by its dependency on life science work, which combined with the black-boxed character of bioinformatic expertise further contributes to situating bioinformatics on the periphery of the life sciences. Finally, the imagined futures of bioinformatic work suggest that bioinformatics will become ever more indispensable without necessarily becoming more visible, forcing bioinformaticians into difficult professional and career choices. Bioinformatic expertise and labour is epistemically central but often institutionally peripheral. In part, this is a result of the ways in which the character, power distribution and potential futures of bioinformatics are constituted. However, alternative paths can be imagined.
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