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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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PLOS Pathogens: Influenza Virus Reassortment Occurs with High Frequency in the Absence of Segment Mismatch

PLOS Pathogens: Influenza Virus Reassortment Occurs with High Frequency in the Absence of Segment Mismatch | Virology and Bioinformatics from Virology.ca | Scoop.it

Reassortment is fundamental to the evolution of influenza viruses and plays a key role in the generation of epidemiologically significant strains. Previous studies indicate that reassortment is restricted by segment mismatch, arising from functional incompatibilities among components of two viruses. Additional factors that dictate the efficiency of reassortment remain poorly characterized. Thus, it is unclear what conditions are favorable for reassortment and therefore under what circumstances novel influenza A viruses might arise in nature. Herein, we describe a system for studying reassortment in the absence of segment mismatch and exploit this system to determine the baseline efficiency of reassortment and the effects of infection dose and timing.

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Smallpox: can we still learn from the journey to eradication?

One of the most celebrated achievements of immunology and modern medicine is the eradication of the dreaded plague smallpox. From the introduction of smallpox vaccination by Edward Jenner, to its popularization by Louis Pasteur, to the eradication effort led by Donald Henderson, this story has many lessons for us today, including the characteristics of the disease and vaccine that permitted its eradication, and the obviousness of the vaccine as a vector for other intractable Infectious diseases. The disease itself, interpreted in the light of modern molecular immunology, is an obvious immunopathological disease, which occurs after a latent interval of 1-2 weeks, and manifests as a systemic cell-mediated delayed type hypersensitivity (DTH) syndrome.

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Virophages, polintons, and transpovirons: a complex evolutionary network of diverse selfish genetic elements with different reproduction strategies

Virophages, polintons, and transpovirons: a complex evolutionary network of diverse selfish genetic elements with different reproduction strategies | Virology and Bioinformatics from Virology.ca | Scoop.it

The results of the phylogenomic analysis of the virophages and related genetic elements are compatible with the concept of network-like evolution of the virus world and emphasize multiple evolutionary connections between bona fide viruses and other classes of capsid-less mobile elements.

Altogether, virophages, polintons, a distinct Tetrahymena transposable element Tlr1, transpovirons, adenoviruses, and some bacteriophages form a network of evolutionary relationships that is held together by overlapping sets of shared genes and appears to represent a distinct module in the vast total network of viruses and mobile elements.


Via Chad Smithson, Ed Rybicki
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Ed Rybicki's curator insight, May 24, 2013 9:26 AM

Blow your MINDS, virologists...deep relationships between phages, human viruses, satellite viruses and big DNA viruses - as well as with diverse mobile elements within genomes.

Ignacio López-Goñi's curator insight, May 25, 2013 3:50 AM

Apasionante: el tema se complica! 

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PLOS Genetics: Hooked and Cooked: A Fish Killer Genome Exposed

PLOS Genetics: Hooked and Cooked: A Fish Killer Genome Exposed | Virology and Bioinformatics from Virology.ca | Scoop.it

Few microorganisms match the impact that the oomycetes have had on mankind. This distinct lineage of eukaryotes is well-known for its most notorious member, Phytophthora infestans, the agent of the nineteenth century Irish potato famine, and several other devastating pathogens of cultivated and wild plants [1]. Indeed, more than 60% of oomycete species infect plants [2]. Less known is the fact that many oomycetes are parasitic on animals, from freshwater fish and crustaceans to mammals, such as livestock, pets, and humans [3]. Animal parasitic oomycetes have received much less attention than their plant pathogenic kin, and our understanding of their virulence mechanisms is rudimentary. However, research momentum is poised to accelerate with the first report of the genome of an animal parasitic oomycete. In this issue of PLOS Genetics, Jiang et al. [4] describe the 63 Mbp genome sequence of the fish pathogen Saprolegnia parasitica and highlight a distinct repertoire of candidate virulence genes.

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PLOS Genetics: Distinctive Expansion of Potential Virulence Genes in the Genome of the Oomycete Fish Pathogen Saprolegnia parasitica

PLOS Genetics: Distinctive Expansion of Potential Virulence Genes in the Genome of the Oomycete Fish Pathogen Saprolegnia parasitica | Virology and Bioinformatics from Virology.ca | Scoop.it

Saprolegnia lacks the large effector families that are hallmarks of plant pathogenic oomycetes, showing evolutionary adaptation to the host. Moreover,Saprolegnia harbors pathogenesis-related genes that were derived by lateral gene transfer from the host and other animal pathogens. The retrotransposon LINE family also appears to be acquired from animal lineages. By transcriptome analysis we show a high rate of allelic variation, which reveals rapidly evolving genes and potentially adaptive evolutionary mechanisms coupled to selective pressures exerted by the animal host

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New phylum of bacteria found lurking in hospital sink’s drain

New phylum of bacteria found lurking in hospital sink’s drain | Virology and Bioinformatics from Virology.ca | Scoop.it
Its genome hints that it may live inside some other organism.
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GALAXY: Web-based visual analysis for high-throughput genomics

Visualization plays an essential role in genomics research by making it possible to observe correlations and trends in large datasets as well as communicate findings to others.
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PLOS Computational Biology: Gag-Pol Processing during HIV-1 Virion Maturation: A Systems Biology Approach

PLOS Computational Biology: Gag-Pol Processing during HIV-1 Virion Maturation: A Systems Biology Approach | Virology and Bioinformatics from Virology.ca | Scoop.it

Proteolytic processing of Gag and Gag-Pol polyproteins by the viral protease (PR) is crucial for the production of infectious HIV-1, and inhibitors of the viral PR are an integral part of current antiretroviral therapy. The process has several layers of complexity (multiple cleavage sites and substrates; multiple enzyme forms; PR auto-processing), which calls for a systems level approach to identify key vulnerabilities and optimal treatment strategies. Here we present the first full reaction kinetics model of proteolytic processing by HIV-1 PR, taking into account all canonical cleavage sites within Gag and Gag-Pol, intermediate products and enzyme forms, enzyme dimerization, the initial auto-cleavage of full-length Gag-Pol as well as self-cleavage of PR. The model allows us to identify the rate limiting step of virion maturation and the parameters with the strongest effect on maturation kinetics. Using the modelling framework, we predict interactions and compensatory potential between individual cleavage rates and drugs, characterize the time course of the process, explain the steep dose response curves associated with PR inhibitors and gain new insights into drug action. While the results of the model are subject to limitations arising from the simplifying assumptions used and from the uncertainties in the parameter estimates, the developed framework provides an extendable open-access platform to incorporate new data and hypotheses in the future.

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Functional interplay between a virus and the ESCRT machinery in Archaea.

Abstract

Recently it has been discovered that a number of eukaryotic viruses, including HIV, coopt the cellular Endosomal Sorting Complex Required for Transport (ESCRT) machinery to affect egress from infected cells. Strikingly, the ESCRT apparatus is conserved in a subset of Archaea, including members of the genus Sulfolobus where it plays a role in cytokinesis. In the current work, we reveal that the archaeal virus Sulfolobus turreted icosahedral virus isolated from Yellowstone National Park's acidic hot springs also exploits the host ESCRT machinery in its replication cycle. Moreover, perturbation of normal ESCRT function abrogates viral replication and, thus, prevents establishment of a productive Sulfolobus turreted icosahedral virus infection. We propose that the Sulfolobus ESCRT machinery is involved in viral assembly within the cytoplasm and in escape from the infected cell by using a unique lysis mechanism. Our results support an ancient origin for viruses “hijacking” ESCRT proteins to complete their replication cycle and thus identify a critical host–virus interaction conserved between two domains of life.

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New method of mass-producing highest-quality oligonucleotides enzymatically

New method of mass-producing highest-quality oligonucleotides enzymatically | Virology and Bioinformatics from Virology.ca | Scoop.it

A new method of manufacturing short, single-stranded DNA molecules can solve many of the problems associated with current production methods.

The new method can be of value to development of drugs consisting of DNA fragments and to DNA nanotechnology research.

 

The novel technique for manufacturing short, single-stranded DNA molecules — or oligonucleotides — has been developed by researchers at Karolinska Institute in Sweden and Harvard University.

 

Such DNA fragments constitute a basic tool for researchers and play a key part in many fields of science. Many of the recent advances in genetic and molecular biological research and development, such as the ability to quickly scan an organism’s genome, would not have been possible without oligonucleotides.

 

The new method is versatile and able to solve problems that currently restrict the production of DNA fragments.

 

“We’ve used enzymatic production methods to create a system that not only improves the quality of the manufactured oligonucleotides but that also makes it possible to scale up production using bacteria in order to produce large amounts of DNA copies cheaply,” says co-developer Björn Högberg at the Swedish Medical Nanoscience Center, part of the Department of Neuroscience at Karolinska Institutet in Sweden.

 

The process of bioproduction, whereby bacteria are used to copy DNA sequences, enables the manufacture of large amounts of DNA copies at a low cost. Unlike current methods of synthesising oligonucleotides, where the number of errors increases with the length of the sequence, this new method according to the developers also works well for long oligonucleotides of several hundred nitrogenous bases.

 

The DNA molecules are first formed as a long string of single-stranded DNA in which the sequence of interest is repeated several times. The long strand forms tiny regions called hairpins, where the strand folds back on itself. These hairpins can then be cut up by enzymes, which serve as a molecular-biological pair of scissors that cuts the DNA at selected sites. Several different oligonucleotides can thus be produced at the same time in a perfectly balanced combination, which is important if they are to be crystallised or used therapeutically.

 

“Oligonucleotide-based drugs are already available, and it’s very possible that our method could be used to produce purer and cheaper versions of these drugs,” says Dr Björn Högberg.


Via Dr. Stefan Gruenwald
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CineversityTV's curator insight, June 7, 2013 12:26 PM

even science has its fools who open Pandora's box even further.

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High-resolution deep sequencing reveals biodiversity, population structure, and persistence of HIV-1 quasispecies within host ecosystems. Retrovirology. 2012

High-resolution deep sequencing reveals biodiversity, population structure, and persistence of HIV-1 quasispecies within host ecosystems. Retrovirology. 2012 | Virology and Bioinformatics from Virology.ca | Scoop.it
BACKGROUND:

Deep sequencing provides the basis for analysis of biodiversity of taxonomically similar organisms in an environment. While extensively applied to microbiome studies, population genetics studies of viruses are limited. To define the scope of HIV-1 population biodiversity within infected individuals, a suite of phylogenetic and population genetic algorithms was applied to HIV-1 envelope hypervariable domain 3 (Env V3) within peripheral blood mononuclear cells from a group of perinatally HIV-1 subtype B infected, therapy-naïve children.

RESULTS:

Biodiversity of HIV-1 Env V3 quasispecies ranged from about 70 to 270 unique sequence clusters across individuals. Viral population structure was organized into a limited number of clusters that included the dominant variants combined with multiple clusters of low frequency variants. Next generation viral quasispecies evolved from low frequency variants at earlier time points through multiple non-synonymous changes in lineages within the evolutionary landscape. Minor V3 variants detected as long as four years after infection co-localized in phylogenetic reconstructions with early transmitting viruses or with subsequent plasma virus circulating two years later.

CONCLUSIONS:

Deep sequencing defines HIV-1 population complexity and structure, reveals the ebb and flow of dominant and rare viral variants in the host ecosystem, and identifies an evolutionary record of low-frequency cell-associated viral V3 variants that persist for years. Bioinformatics pipeline developed for HIV-1 can be applied for biodiversity studies of virome populations in human, animal, or plant ecosystems.

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Viral and Host Factors Required for Avian H5N1 Influenza A Virus Replication in Mammalian Cells. Viruses. 2013

Following the initial and sporadic emergence into humans of highly pathogenic avian H5N1 influenza A viruses in Hong Kong in 1997, we have come to realize the potential for avian influenza A viruses to be transmitted directly from birds to humans. Understanding the basic viral and cellular mechanisms that contribute to infection of mammalian species with avian influenza viruses is essential for developing prevention and control measures against possible future human pandemics. Multiple physical and functional cellular barriers can restrict influenza A virus infection in a new host species, including the cell membrane, the nuclear envelope, the nuclear environment, and innate antiviral responses. In this review, we summarize current knowledge on viral and host factors required for avian H5N1 influenza A viruses to successfully establish infections in mammalian cells. We focus on the molecular mechanisms underpinning mammalian host restrictions, as well as the adaptive mutations that are necessary for an avian influenza virus to overcome them. It is likely that many more viral and host determinants remain to be discovered, and future research in this area should provide novel and translational insights into the biology of influenza virus-host interactions.

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#NGS Developments in next generation sequencing – a visualisation

#NGS Developments in next generation sequencing – a visualisation | Virology and Bioinformatics from Virology.ca | Scoop.it
With this post I present a figure I’ve been working on for a while now. With it, I try to summarise the developments in (next generation) sequencing, or at least a few aspects of it. I’...

Via César Augusto Medina Culma
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Luminous bacterial proteins detect chemicals in water

Luminous bacterial proteins detect chemicals in water | Virology and Bioinformatics from Virology.ca | Scoop.it
Scientists have developed a simple color sensor principle which facilitates the detection of residual medications, trace metals from industrial process waters, and many other substances.
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Extreme virus resistance in plants

Extreme virus resistance in plants | Virology and Bioinformatics from Virology.ca | Scoop.it
When a virus infects a plant, a slient war rages, fought with RNA weapons.
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What is needed for phage therapy to become a reality in Western medicine?

What is needed for phage therapy to become a reality in Western medicine? | Virology and Bioinformatics from Virology.ca | Scoop.it

The current status of phage therapy approaches is reviewed and possible hurdles to a practical medical application of bacteriophages in Western countries are identified as discussed at a recent EMBO meeting on “Viruses of Microbes” in Brussels. In view of the growing antibiotic resistance crisis, a coordinated effort by the public health sector is needed to evaluate the potential of phage therapy as an adjunct to antibiotics.

 T4 coliphage picture by Russell Kightley Media


Via Ed Rybicki
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Ed Rybicki's curator insight, May 29, 2013 10:45 AM

 

 I missed this first time around - but it is one of the most-downloaded papers from Virology, so probably well worth a read.Or getting into the field...?
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Google Maps Engine Lite - Create Advanced Custom Google Maps

Google Maps Engine Lite - Create Advanced Custom Google Maps | Virology and Bioinformatics from Virology.ca | Scoop.it

Any use in the bioinformatics arena???

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Medicago “first in the world” to report positive pre-clinical data for H7N9 vaccine

Medicago “first in the world” to report positive pre-clinical data for H7N9 vaccine | Virology and Bioinformatics from Virology.ca | Scoop.it
Medicago has announced that it is “first in the world” to report positive interim results from a pre-clinical trial for an H7N9 Virus-Like Particle (VLP)
Ed Rybicki's insight:

Love it!  Going Green: the sensible thing to do.

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US Supreme Court bans DNA patents

US Supreme Court bans DNA patents | Virology and Bioinformatics from Virology.ca | Scoop.it
Human genes may not be patented, but artificially copied DNA can be intellectual property, the US Supreme Court rules unanimously.
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BMC Genomics | Abstract | Web-based visual analysis for high-throughput genomics

Visualization plays an essential role in genomics research by making it possible to observe correlations and trends in large datasets as well as communicate findings to others. Visual analysis, which combines visualization with analysis tools to enable seamless use of both approaches for scientific investigation, offers a powerful method for performing complex genomic analyses. However, there are numerous challenges that arise when creating rich, interactive Web-based visualizations/visual analysis applications for high-throughput genomics. These challenges include managing data flow from Web server to Web browser, integrating analysis tools and visualizations, and sharing visualizations with colleagues

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PLOS Biology: Virions at the Gates: Receptors and the Host–Virus Arms Race

PLOS Biology: Virions at the Gates: Receptors and the Host–Virus Arms Race | Virology and Bioinformatics from Virology.ca | Scoop.it

All viruses need to bind to specific receptor molecules on the surface of target cells to initiate infection. Virus–receptor binding is highly specific, and this specificity determines both the species and the cell type that can be infected by a given virus. In some well-studied cases, the virus-binding region on the receptor has been found to be unrelated to the receptor's normal cellular function. Resistance to virus infection can thus evolve by selection of mutations that alter amino acids in the binding region with minimal effect on normal function. This sort of positive selection can be used to infer the history of the host–virus “arms race” during their coevolution.

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PLOS Pathogens: Cryotomography of Budding Influenza A Virus Reveals Filaments with Diverse Morphologies that Mostly Do Not Bear a Genome at Their Distal End

PLOS Pathogens: Cryotomography of Budding Influenza A Virus Reveals Filaments with Diverse Morphologies that Mostly Do Not Bear a Genome at Their Distal End | Virology and Bioinformatics from Virology.ca | Scoop.it
Abstract

Influenza viruses exhibit striking variations in particle morphology between strains. Clinical isolates of influenza A virus have been shown to produce long filamentous particles while laboratory-adapted strains are predominantly spherical. However, the role of the filamentous phenotype in the influenza virus infectious cycle remains undetermined. We used cryo-electron tomography to conduct the first three-dimensional study of filamentous virus ultrastructure in particles budding from infected cells. Filaments were often longer than 10 microns and sometimes had bulbous heads at their leading ends, some of which contained tubules we attribute to M1 while none had recognisable ribonucleoprotein (RNP) and hence genome segments. Long filaments that did not have bulbs were infrequently seen to bear an ordered complement of RNPs at their distal ends. Imaging of purified virus also revealed diverse filament morphologies; short rods (bacilliform virions) and longer filaments. Bacilliform virions contained an ordered complement of RNPs while longer filamentous particles were narrower and mostly appeared to lack this feature, but often contained fibrillar material along their entire length. The important ultrastructural differences between these diverse classes of particles raise the possibility of distinct morphogenetic pathways and functions during the infectious process.

 

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Genetic variability among complete human respiratory syncytial virus subgroup A genomes: bridging molecular evolutionary dynamics and epidemiology. PLoS One. 2012

Human respiratory syncytial virus (RSV) is an important cause of severe lower respiratory tract infections in infants and the elderly. In the vast majority of cases, however, RSV infections run mild and symptoms resemble those of a common cold. The immunological, clinical, and epidemiological profile of severe RSV infections suggests a disease caused by a virus with typical seasonal transmission behavior, lacking clear-cut virulence factors, but instead causing disease by modifying the host's immune response in a way that stimulates pathogenesis. Yet, the interplay between RSV-evoked immune responses and epidemic behavior, and how this affects the genomic evolutionary dynamics of the virus, remains poorly understood. Here, we present a comprehensive collection of 33 novel RSV subgroup A genomes from strains sampled over the last decade, and provide the first measurement of RSV-A genomic diversity through time in a phylodynamic framework. In addition, we map amino acid substitutions per protein to determine mutational hotspots in specific domains. Using Bayesian genealogical inference, we estimated the genomic evolutionary rate to be 6.47 × 10(-4) (credible interval: 5.56 × 10(-4), 7.38 × 10(-4)) substitutions/site/year, considerably slower than previous estimates based on G gene sequences only. The G gene is however marked by elevated substitution rates compared to other RSV genes, which can be attributed to relaxed selective constraints. In line with this, site-specific selection analyses identify the G gene as the major target of diversifying selection. Importantly, statistical analysis demonstrates that the immune driven positive selection does not leave a measurable imprint on the genome phylogeny, implying that RSV lineage replacement mainly follows nonselective epidemiological processes. The roughly 50 years of RSV-A genomic evolution are characterized by a constant population size through time and general co-circulation of lineages over many epidemic seasons - a conclusion that might be taken into account when developing future therapeutic and preventive strategies.

  
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Quantifying pathogen surveillance using temporal genomic data. MBio. 2013

With the advent of deep sequencing, genomic surveillance has become a popular method for detection of infectious disease, supplementing information gathered by classic clinical or serological techniques to identify host-determinant markers and trace the origin of transmission. However, two main factors complicate genomic surveillance. First, pathogens exhibiting high genetic diversity demand higher levels of scrutiny to obtain an accurate representation of the entire population. Second, current systems of detection are nonuniform, with significant gaps in certain geographic locations and animal reservoirs. Despite past unforeseen pandemics like the 2009 swine-origin H1N1 influenza virus, there is no standardized way of evaluating surveillance. A more complete surveillance system should capture a greater proportion of pathogen diversity. Here we present a novel quantitative method of assessing the completeness of genomic surveillance that incorporates the time of sequence collection, as well as the pathogen's evolutionary rate. We propose the q2 coefficient, which measures the proportion of sequenced isolates whose closest neighbor in the past is within a genetic distance equivalent to 2 years of evolution, roughly the median time of changing strain selection for influenza A vaccines. Easily interpretable and significantly faster than other methods, the q2 coefficient requires no full phylogenetic characterization or use of arbitrary clade definitions. Application of the q2 coefficient to influenza A virus confirmed poor sampling of swine and avian populations and identified regions with deficient surveillance. We demonstrate that the q2 coefficient can not only be applied to other pathogens, including dengue and West Nile viruses, but also used to describe surveillance dynamics, particularly the effects of different public health policies.

IMPORTANCE:

Surveillance programs have become key assets in determining the emergence or prevalence of pathogens circulating in human and animal populations. Genomic surveillance, in particular, provides comprehensive information on the history of isolates and potential molecular markers for infectivity and pathogenicity. Current techniques for evaluating genomic surveillance are inaccurate, ignoring the pathogen's evolutionary rate and biodiversity, as well as the timing of sequence collection. Using sequence data, we propose the q2 coefficient as a quantitative measure of surveillance completeness that combines elements of time and evolution without defining arbitrary criteria for clades or species. Through several case studies of influenza A, dengue, and West Nile viruses, we employed the q2 coefficient to identify sampling deficiencies in different host species and locations, as well as examine the effects of different public health policies through historical records of the q2 coefficient. These results can guide public health agencies to focus resource allocation and virus collection to bolster specific problems in surveillance.

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Design of a set of probes with high potential... Bioinformation. 2013

An Influenza Probe Set (IPS) consisting in 1,249 9-mer probes for genomic fingerprinting of closely and distantly related Influenza Virus strains was designed and tested in silico. The IPS was derived from alignments of Influenza genomes. The RNA segments of 5,133 influenza strains having diverse degree of relatedness were concatenated and aligned. After alignment, 9-mer sites having high Shannon entropy were searched. Additional criteria such as: G+C content between 35 to 65%, absence of dimer or trimer consecutive repeats, a minimum of 2 differences between 9mers and selecting only sequences with Tm values between 34.5 and 36.5oC were applied for selecting probes with high sequential entropy. Virtual Hybridization was used to predict Genomic Fingerprints to assess the capability of the IPS to discriminate between influenza and related strains. Distance scores between pairs of Influenza Genomic Fingerprints were calculated, and used for estimating Taxonomic Trees. Visual examination of both Genomic Fingerprints and Taxonomic Trees suggest that the IPS is able to discriminate between distant and closely related Influenza strains. It is proposed that the IPS can be used to investigate, by virtual or experimental hybridization, any new, and potentially virulent, strain.

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