Virology and Bioinformatics from Virology.ca
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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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Sequence Analysis of In Vivo Defective Interfering-Like RNA of Influenza A H1N1 Pandemic Virus

Influenza virus defective interfering (DI) particles are naturally occurring noninfectious virions typically generated during in vitro serial passages in cell culture of the virus at a high multiplicity of infection. DI particles are recognized for the role they play in inhibiting viral replication and for the impact they have on the production of infectious virions. To date, influenza virus DI particles have been reported primarily as a phenomenon of cell culture and in experimentally infected embryonated chicken eggs. They have also been isolated from a respiratory infection of chickens. Using a sequencing approach, we characterize several subgenomic viral RNAs from human nasopharyngeal specimens infected with the influenza A(H1N1)pdm09 virus. The distribution of these in vivo-derived DI-like RNAs was similar to that of in vitro DIs, with the majority of the defective RNAs generated from the PB2 (segment 1) of the polymerase complex, followed by PB1 and PA. The lengths of the in vivo-derived DI-like segments also are similar to those of known in vitro DIs, and the in vivo-derived DI-like segments share internal deletions of the same segments. The presence of identical DI-like RNAs in patients linked by direct contact is compatible with transmission between them. The functional role of DI-like RNAs in natural infections remains to be established.

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Inhibition of hepatitis B virus (HBV) gene expression and replication by HBx gene silencing in a hydrodynamic injection mouse model with a new clone of HBV genotype B

It has been suggested that different hepatitis B virus (HBV) genotypes may have distinct virological characteristics that correlate with clinical outcomes during antiviral therapy and the natural course of infection.
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PLOS Pathogens: Deciphering the Cryptic Genome: Genome-wide Analyses of the Rice Pathogen Fusarium fujikuroi Reveal Complex Regulation of Secondary Metabolism and Novel Metabolites

PLOS Pathogens: Deciphering the Cryptic Genome: Genome-wide Analyses of the Rice Pathogen Fusarium fujikuroi Reveal Complex Regulation of Secondary Metabolism and Novel Metabolites | Virology and Bioinformatics from Virology.ca | Scoop.it

 Comparison of the F. fujikuroi genome to those of six other fusaria revealed that only a small number of gene clusters are conserved among these species, thus providing new insights into the divergence of secondary metabolism in the genus Fusarium. Noteworthy, GA biosynthetic genes are present in some related species, but GA biosynthesis is limited to F. fujikuroi, suggesting that this provides a selective advantage during infection of the preferred host plant rice. Among the genome sequences analyzed, one cluster that includes a polyketide synthase gene (PKS19) and another that includes a non-ribosomal peptide synthetase gene (NRPS31) are unique to F. fujikuroi. The metabolites derived from these clusters were identified by HPLC-FTMS-based analyses of engineered F. fujikuroi strains overexpressing cluster genes. In planta expression studies suggest a specific role for the PKS19-derived product during rice infection.From molecules to physiology.

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Association between adverse clinical outcome in human disease caused by novel influenza A H7N9 virus and sustained viral shedding and emergence of antiviral resistance - Lancet

Background

On March 30, a novel influenza A subtype H7N9 virus (A/H7N9) was detected in patients with severe respiratory disease in eastern China. Virological factors associated with a poor clinical outcome for this virus remain unclear. We quantified the viral load and analysed antiviral resistance mutations in specimens from patients with A/H7N9.

Methods

We studied 14 patients with A/H7N9 disease admitted to the Shanghai Public Health Clinical Centre (SPHCC), China, between April 4, and April 20, 2013, who were given antiviral treatment (oseltamivir or peramivir) for less than 2 days before admission. We investigated the viral load in throat, stool, serum, and urine specimens obtained sequentially from these patients. We also sequenced viral RNA from these specimens to study the mutations associated with resistance to neuraminidase inhibitors and their association with disease outcome.

Findings

All patients developed pneumonia, seven of them required mechanical ventilation, and three of them further deteriorated to become dependent on extracorporeal membrane oxygenation (ECMO), two of whom died. Antiviral treatment was associated with a reduction of viral load in throat swab specimens in 11 surviving patients. Three patients with persistently high viral load in the throat in spite of antiviral therapy became ECMO dependent. An Arg292Lys mutation in the virus neuraminidase (NA) gene known to confer resistance to both zanamivir and oseltamivir was identified in two of these patients, both also received corticosteroid treatment. In one of them, wild-type sequence Arg292 was noted 2 days after start of antiviral treatment, and the resistant mutant Lys292 dominated 9 days after start of treatment.

Interpretation

Reduction of viral load following antiviral treatment correlated with improved outcome. Emergence of NA Arg292Lys mutation in two patients who also received corticosteroid treatment led to treatment failure and a poor clinical outcome. The emergence of antiviral resistance in A/H7N9 viruses, especially in patients receiving corticosteroid therapy, is concerning, needs to be closely monitored, and considered in pandemic preparedness planning.

 
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Lack of Association of Guillain-Barré Syndrome with Vaccinations

Lack of Association of Guillain-Barré Syndrome with Vaccinations | Virology and Bioinformatics from Virology.ca | Scoop.it

Shortly after getting a vaccination, people are no more likely to develop a dangerous nerve-damaging condition called Guillain-Barré syndrome, or GBS, than they are at other times, a new analysis finds.

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PLOS Pathogens: Dissection of Antibody Specificities Induced by Yellow Fever Vaccination

PLOS Pathogens: Dissection of Antibody Specificities Induced by Yellow Fever Vaccination | Virology and Bioinformatics from Virology.ca | Scoop.it

The live-attenuated yellow fever vaccine has been administered to more than 600 million people worldwide and is considered to be one of the most successful viral vaccines ever produced. Following injection, the apathogenic vaccine virus replicates in the vaccinee and induces antibodies that mediate virus neutralization and subsequent protection from disease. In principle, many different antibodies are induced by viral antigens, but it is becoming increasingly clear that only a subset of them is capable of inactivating the virus, and some antibody populations appear to dominate the immune response. However, to date there has been very little information on individual-specific variations of immunodominance and how such variations can affect the functionality of antibody responses. In our study, we addressed these issues and analyzed the fine specificities of antibodies induced by YF vaccination as well as the contribution of different antibody subsets to virus neutralization in 51 vaccinees. We demonstrate an extensive degree of individual variation with respect to immunodominance of antibody populations and their contribution to virus neutralization. Such variations can have an impact on vaccine-mediated protection, and thus insight into this phenomenon can provide leads for novel strategies in modern vaccine design.

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Researchers strike gold with nanotech vaccine

Researchers strike gold with nanotech vaccine | Virology and Bioinformatics from Virology.ca | Scoop.it
Scientists in the US have developed a novel vaccination method that uses tiny gold particles to mimic a virus and carry specific proteins to the body’s specialist immune cells.
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Nucleotide substitutions in dengue virus serotypes from Asian and American countries: insights into intracodon recombination and purifying selection BMC Microbiol. 2013

Dengue virus (DENV) infection represents a significant public health problem in many subtropical and tropical countries. Although genetically closely related, the four serotypes of DENV differ in antigenicity for which cross protection among serotypes is limited. It is also believed that both multi-serotype infection as well as the evolution of viral antigenicity may have confounding effects in increased dengue epidemics. Numerous studies have been performed that investigated genetic diversity of DENV, but the precise mechanism(s) of dengue virus evolution are not well understood.

RESULTS:

We investigated genome-wide genetic diversity and nucleotide substitution patterns in the four serotypes among samples collected from different countries in Asia and Central and South America and sequenced as part of the Genome Sequencing Center for Infectious Diseases at the Broad Institute. We applied bioinformatics, statistical and coalescent simulation methods to investigate diversity of codon sequences of DENV samples representing the four serotypes. We show that fixation of nucleotide substitutions is more prominent among the inter-continental isolates (Asian and American) of serotypes 1, 2 and 3 compared to serotype 4 isolates (South and Central America) and are distributed in a non-random manner among the genes encoded by the virus. Nearly one third of the negatively selected sites are associated with fixed mutation sites within serotypes. Our results further show that of all the sites showing evidence of recombination, the majority (~84%) correspond to sites under purifying selection in the four serotypes. The analysis further shows that genetic recombination occurs within specific codons, albeit with low frequency (< 5% of all recombination sites) throughout the DENV genome of the four serotypes and reveals significant enrichment (p < 0.05) among sites under purifying selection in the virus.

CONCLUSION:

The study provides the first evidence for intracodon recombination in DENV and suggests that within codons, genetic recombination has a significant role in maintaining extensive purifying selection of DENV in natural populations. Our study also suggests that fixation of beneficial mutations may lead to virus evolution via translational selection of specific sites in the DENV genome.

  
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Vaccination induced antibodies to recombinant avian influenza a virus M2 protein or synthetic M2e peptide do not bind to the M2 protein on the virus or virus infected ...

Influenza viruses are characterized by their highly variable surface proteins HA and NA. The third surface protein M2 is a nearly invariant protein in all Influenza A strains.
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Virology Journal | Abstract | Atypical hand-foot-mouth disease in children: a hospital-based prospective cohort study

In 2010, we observed children with atypical presentations of hand-foot-mouth disease (HFMD), such as rashes on earlobes and faces, or bullae on trunks and bilateral limbs. Hyperpigmentation later developed as the bullous lesions crusted.
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Receptor binding by an H7N9 influenza virus from humans. Nature. 2013

Of the 132 people known to have been infected with H7N9 influenza viruses in China, 37 died, and many were severely ill. Infection seems to have involved contact with infected poultry. We have examined the receptor-binding properties of this H7N9 virus and compared them with those of an avian H7N3 virus. We find that the human H7 virus has significantly higher affinity for α-2,6-linked sialic acid analogues ('human receptor') than avian H7 while retaining the strong binding to α-2,3-linked sialic acid analogues ('avian receptor') characteristic of avian viruses. The human H7 virus does not, therefore, have the preference for human versus avian receptors characteristic of pandemic viruses. X-ray crystallography of the receptor-binding protein, haemagglutinin (HA), in complex with receptor analogues indicates that both human and avian receptors adopt different conformations when bound to human H7 HA than they do when bound to avian H7 HA. Human receptor bound to human H7 HA exits the binding site in a different direction to that seen in complexes formed by HAs from pandemic viruses and from an aerosol-transmissible H5 mutant. The human-receptor-binding properties of human H7 probably arise from the introduction of two bulky hydrophobic residues by the substitutions Gln226Leu and Gly186Val. The former is shared with the 1957 H2 and 1968 H3 pandemic viruses and with the aerosol-transmissible H5 mutant. We conclude that the human H7 virus has acquired some of the receptor-binding characteristics that are typical of pandemic viruses, but its retained preference for avian receptor may restrict its further evolution towards a virus that could transmit efficiently between humans, perhaps by binding to avian-receptor-rich mucins in the human respiratory tract rather than to cellular receptors.

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Cytoplasmic RNA viruses as potential vehicles for the delivery of therapeutic small RNAs

Cytoplasmic RNA viruses as potential vehicles for the delivery of therapeutic small RNAs | Virology and Bioinformatics from Virology.ca | Scoop.it

Viral vectors have become the best option for the delivery of therapeutic genes in conventional and RNA interference-based gene therapies. The current viral vectors for the delivery of small regulatory RNAs are based on DNA viruses and retroviruses/lentiviruses. Cytoplasmic RNA viruses have been excluded as viral vectors for RNAi therapy because of the nuclear localization of the microprocessor complex and the potential degradation of the viral RNA genome during the excision of any virus-encoded pre-microRNAs. However, in the last few years, the presence of several species of small RNAs (e.g., virus-derived small interfering RNAs, virus-derived short RNAs, and unusually small RNAs) in animals and cell cultures that are infected with cytoplasmic RNA viruses has suggested the existence of a non-canonical mechanism of microRNA biogenesis. Several studies have been conducted on the tick-borne encephalitis virus and on the Sindbis virus in which microRNA precursors were artificially incorporated and demonstrated the production of mature microRNAs. The ability of these viruses to recruit Drosha to the cytoplasm during infection resulted in the efficient processing of virus-encoded microRNA without the viral genome entering the nucleus. In this review, we discuss the relevance of these findings with an emphasis on the potential use of cytoplasmic RNA viruses as vehicles for the efficient delivery of therapeutic small RNAs.

 
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A novel dengue virus detection method that couples DNAzyme and gold nanoparticle approaches

Recent epidemics of dengue viruses (DENV) coupled with new outbreaks on the horizon have renewed the demand for novel detection methods that have the ability to identify this viral pathogen prior to the manifestation of symptoms.
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Viruses in commercial cell lines

Viruses in commercial cell lines | Virology and Bioinformatics from Virology.ca | Scoop.it

Cryopreserved primary human renal proximal tubule epithelial cells (RPTEC) were obtained from a commercial supplier for studies of Simian virus 40 (SV40). Within twelve hrs after cell cultures were initiated, cytoplasmic vacuoles appeared in many of the RPTEC. The RPTEC henceforth deteriorated rapidly. Since SV40 induces the formation of cytoplasmic vacuoles, this batch of RPTEC was rejected for the SV40 study. Nevertheless, we sought the likely cause(s) of the deterioration of the RPTEC as part of our technology development efforts.

 

 

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Ed Rybicki's curator insight, July 1, 2013 10:53 AM

ALWAYS check your reagents....

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#overlyhonestmethods in science research - #funny (to some)

Imgur is used to share photos with social networks and online communities, and has the funniest pictures from all over the Internet.
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Mel Melendrez-Vallard's curator insight, June 28, 2013 4:31 PM

you have to laugh...i did.

Ed Rybicki's comment, July 1, 2013 10:56 AM
"The sample was incubated at room temperature for 36 hours because the student forgot it on the bench, went out and got drunk, and was too hungover to come in the following day". Actually happened...B-)
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The roles of competition and mutation in shaping antigenic and genetic diversity in influenza PLoS Pathog. 2013

Influenza A (H3N2) offers a well-studied, yet not fully understood, disease in terms of the interactions between pathogen population dynamics, epidemiology and genetics. A major open question is why the virus population is globally dominated by a single and very recently diverged (2-8 years) lineage. Classically, this has been modeled by limiting the generation of new successful antigenic variants, such that only a small subset of progeny acquire the necessary mutations to evade host immunity. An alternative approach was recently suggested by Recker et al. in which a limited number of antigenic variants are continuously generated, but most of these are suppressed by pre-existing host population immunity. Here we develop a framework spanning the regimes described above to explore the impact of rates of mutation and levels of competition on phylodynamic patterns. We find that the evolutionary dynamics of the subtype H3N2 influenza is most easily generated within this framework when it is mutation limited as well as being under strong immune selection at a number of epitope regions of limited diversity.

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PLOS Pathogens: Extreme Genetic Fragility of the HIV-1 Capsid

PLOS Pathogens: Extreme Genetic Fragility of the HIV-1 Capsid | Virology and Bioinformatics from Virology.ca | Scoop.it

The HIV-1 capsid protein (CA) is absolutely essential for viral replication and there is, therefore, intense evolutionary pressure for HIV-1 CA to conserve its functions. However, HIV-1 CA is also a key target of the host immune response, which should provide evolutionary pressure to diversify CA sequence. Genetic robustness, or fragility, is defined as the ability, or lack thereof, of a biological entity to preserve function in the face of sequence changes. Thus, it should be advantageous to HIV-1 CA to evolve genetic robustness. Here, we present the results of extensive, random mutagenesis of single amino acids in CA that reveal an extreme genetic fragility. Although CA participates in several steps in HIV-1 replication, the biological basis for its genetic fragility was primarily the need to participate in the efficient and proper assembly of mature virion particles. The extreme genetic fragility of HIV-1 CA may be one reason why immune responses to it correlate with better prognosis in HIV-1 infection, and suggests that CA is a good target for therapy and vaccination strategies.

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How TO Host A Scoopit Newsletter / Landing Page FREE on Google Drive or Dropbox

How TO Host A Scoopit Newsletter / Landing Page FREE on Google Drive or Dropbox | Virology and Bioinformatics from Virology.ca | Scoop.it
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Bonnie Bracey Sutton's comment, September 16, 2013 8:26 AM
Found A Cool Use for Scoop.it's new Newsletter feature. It is easy to create a content landing page and host it free with Google Drive.

Here's How...

1. Create a newsletter using the Manage > Create A Newsletter

2. Download as a Zip file. Open the Zip file.

3. Upload the HTML file to your Google drive into a public folder.

4. Click on the HTML file. A window pops up, click on OPEN in lower right corner.

5. Click on preview. Copy the URL that appears in the browser window:
https://googledrive.com/host/0B0eG3a8zValDQjl6aldwQlJMNDg/email%203.html ;
Alfredo Corell's curator insight, September 22, 2013 2:42 PM
Martin (Marty) Smith's insight:

Found A Cool Use for Scoop.it's new Newsletter feature. It is easy to create a content landing page and host it free with Google Drive. 

Here's How...

1. Create a newsletter using the Manage > Create A Newsletter

 

2. Download as a Zip file. Open the Zip file.

 

3. Upload the HTML file to your Google drive into a public folder.

 

4. Click on the HTML file. A window pops up, click on OPEN in lower right corner. 

 

5. Click on preview. Copy the URL that appears in the browser window:

https://googledrive.com/host/0B0eG3a8zValDQjl6aldwQlJMNDg/email%203.html ;

Next figuring out how to add a Call To Action and subscription code.  BTW, Unbounce charges $700 a year to host landing pages :). 

 

Also works on DropBox. 

The Free Alternative
The interesting question is could you create a web marketing business with NO money for websites or blogs? Yes is the answer to that question. By using free tools such as Google Drive, Scoop.it and Blogger or WordPress you could create a business without paying anything to web development. 

You might find that business is limited in scale, but so what. Your cost is  limited to your sweat equity to create a revenue stream and THEN buy the website improvements you need to go to the next level. I just build a MagentoGo store (Story of Cancer Store: http://storyofcancer.gostorego.com/ ;) and the same thing is ALMOST true for Ecom.

 

Between Storify, Volusion and Magento you can create a store for sweat equity + $500 (give or take). My little store has already made $130 inside of its first month so well on its way to paying for its serving costs. 

The ultimate lesson of crowdfunding and crowdsourcing is DO NOTHING until it is worth the investment to do so :). 

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BMC Medicine | Abstract | Comparing influenza vaccine efficacy against mismatched and matched strains: a systematic review and meta-analysis

Influenza vaccines are most effective when the antigens in the vaccine match those of circulating strains. However, antigens contained in the vaccines do not always match circulating strains.
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Mel Melendrez-Vallard's curator insight, June 27, 2013 7:21 PM

a good way to 'catch up'

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Virus assembly and maturation: auto-regulation through allosteric molecular switches J Mol Biol. 2013

We generalize the concept of allostery from the traditional non-active-site control of enzymes to virus maturation. Virtually, all animal viruses transition from a procapsid noninfectious state to a mature infectious state. The procapsid contains an encoded chemical program that is executed following an environmental cue. We developed an exceptionally accessible virus system for the study of the activators of maturation and the downstream consequences that result in particle stability and infectivity. Nudaurelia capensis omega virus (NωV) is a T=4 icosahedral virus that undergoes a dramatic maturation in which the 490-Å spherical procapsid condenses to a 400-Å icosahedral-shaped capsid with associated specific auto-proteolysis and stabilization. Employing X-ray crystallography, time-resolved electron cryo-microscopy and hydrogen/deuterium exchange as well as biochemistry, it was possible to define the mechanisms of allosteric communication among the four quasi-equivalent subunits in the icosahedral asymmetric unit. These gene products undergo proteolysis at different rates, dependent on quaternary structure environment, while particle stability is conferred globally following only a few local subunit transitions. We show that there is a close similarity between the concepts of tensegrity (associated with geodesic domes and mechanical engineering) and allostery (associated with biochemical control mechanisms).

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Overexpression of PRMT6 does not suppress HIV-1 Tat transactivation in cells naturally lacking PRMT6

Protein arginine methyltransferase 6 (PRMT6) can methylate the HIV-1 Tat, Rev and nucleocapsid proteins in a manner that diminishes each of their functions in in vitro assays, and increases the stability of Tat in human cells.
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Genetic Requirement for Hemagglutinin Glycosylation and Its Implications for Influenza A H1N1 Virus Evolution

Genetic Requirement for Hemagglutinin Glycosylation and Its Implications for Influenza A H1N1 Virus Evolution | Virology and Bioinformatics from Virology.ca | Scoop.it

Influenza A virus has evolved and thrived in human populations. Since the 1918 influenza A pandemic, human H1N1 viruses had acquired additional N-linked glycosylation (NLG) sites within the globular head region of hemagglutinin (HA) until the NLG-free HA head pattern of the 1918 H1N1 virus was renewed with the swine-derived 2009 pandemic H1N1 virus. Moreover, the HA of the 2009 H1N1 virus appeared to be antigenically related to that of the 1918 H1N1 virus.

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Medicago successfully produces plant-based Rotavirus VLP vaccine candidate

Medicago successfully produces plant-based Rotavirus VLP vaccine candidate | Virology and Bioinformatics from Virology.ca | Scoop.it

Medicago Inc., a biopharmaceutical company focused on developing highly effective and competitive vaccines based on proprietary manufacturing technologies and Virus-Like Particles (VLPs), today announced the successful production of a Rotavirus VLP vaccine candidate comprising all four structural antigens of rotavirus (VP2, VP4, VP6 and VP7) using Medicago's plant-based manufacturing platform.

Medicago also announced today that an international patent application under the Patent Cooperation Treaty (PCT) that broadly covers plant-produced Rotavirus VLPs has been filed.

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Ed Rybicki's curator insight, June 25, 2013 10:38 AM

Going green: how very sensible!