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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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Cytomegalovirus load in whole blood is more reliable for predicting and assessing CMV disease than pp65 antigenaemia

Cytomegalovirus load in whole blood is more reliable for predicting and assessing CMV disease than pp65 antigenaemia | Virology and Bioinformatics from Virology.ca | Scoop.it

CMV is a common cause of disease in immunocompromised patients. Because sampling of the diseased organ can be invasive, markers of systemic CMV reactivation such as pp65 and CMV viral load are commonly used to monitor patients at risk of CMV disease. In this retrospective analysis, the performance of these markers was compared in solid organ transplant recipients, patients with haematological malignancies and HIV infection. Both assays were sensitive markers of reactivation, however, the predictive value for disease of a positive result for both was low. Compared to viral load, the pp65 assay was a less sensitive marker of CMV reactivation. It was only positive when the viral load was greater than 3 log (10) copies/ml whole blood and was negative in 10 instances when the viral load was between 3 and 5 logs. In concordantly positive samples, the number of pp65 positive cells varied widely relative to the viral load and the number of positive cells counted could not be used to predict disease likelihood with any certainty. To conclude, CMV viral load provides a more consistent guide to determine likelihood of disease than pp65 count and is a more sensitive marker of CMV reactivation.

 Herpesvirus graphic by Russell Kightley Media

Ed Rybicki's insight:

It gives me great peasure to tout this paper by my Medical School colleagues - for a nice piece of work which should improve C[yto]MV detection.  Because CMV is cucmber mosaic virus, obviously, and no-one cares about that.  Except cucmbers.

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Herpes Virus Genome, The Pressure Is On

Abstract

 

Herpes simplex virus type 1 (HSV-1) packages its micrometers-long double-stranded DNA genome into a nanometer-scale protein shell, termed the capsid. Upon confinement within the capsid, neighboring DNA strands experience repulsive electrostatic and hydration forces as well as bending stress associated with the tight curvature required of packaged DNA. By osmotically suppressing DNA release from HSV-1 capsids, we provide the first experimental evidence of a high internal pressure of tens of atmospheres within a eukaryotic human virus, resulting from the confined genome. Furthermore, the ejection is progressively suppressed by increasing external osmotic pressures, which reveals that internal pressure is capable of powering ejection of the entire genome from the viral capsid. Despite billions of years of evolution separating eukaryotic viruses and bacteriophages, pressure-driven DNA ejection has been conserved. This suggests it is a key mechanism for viral infection and thus presents a new target for antiviral therapies.

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Oyster deaths linked to hot weather

Oyster deaths linked to hot weather | Virology and Bioinformatics from Virology.ca | Scoop.it
A number of oysters have been killed following the outbreak of a virus in Carlingford Lough in County Down, linked to recent hot weather.
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Close Relative of Human Middle East Respiratory Syndrome Coronavirus in Bat, South Africa (Emerg Infect Dis., edited)

Close Relative of Human Middle East Respiratory Syndrome Coronavirus in Bat, South Africa (Emerg Infect Dis., edited) | Virology and Bioinformatics from Virology.ca | Scoop.it
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Medical Virology of Hepatitis B: how it began and where we are now?

Infection with hepatitis B virus (HBV) may lead to acute or chronic hepatitis. HBV infections were previously much more frequent but there are still 240 million chronic HBV carriers today and ca.
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Defensive Bacteriome Symbiont with a Drastically Reduced Genome

Defensive Bacteriome Symbiont with a Drastically Reduced Genome | Virology and Bioinformatics from Virology.ca | Scoop.it

Strikingly, 15% of the small Profftella genome encoded horizontally acquired genes for synthesizing a novel polyketide toxin. The toxin was extracted, pharmacologically and structurally characterized, and designated diaphorin. The presence of Profftella and its diaphorin-biosynthetic genes was perfectly conserved in the world’s D. citri populations.

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Granulocyte-Macrophage Colony-Stimulating Factor-Armed Oncolytic Measles Virus Is an Effective Therapeutic Cancer Vaccine

Granulocyte-Macrophage Colony-Stimulating Factor-Armed Oncolytic Measles Virus Is an Effective Therapeutic Cancer Vaccine | Virology and Bioinformatics from Virology.ca | Scoop.it

Oncolytic measles viruses (MV) derived from the live attenuated vaccine strain have been engineered for increased antitumor activity, and are currently under investigation in clinical phase 1 trials. Approaches with other viral vectors have shown that insertion of immunomodulatory transgenes enhances the therapeutic potency. In this study, we engineered MV for expression of the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF). For the first time, therapeutic efficacy and adaptive immune response in the context of MV oncolysis could be evaluated in the previously established immunocompetent murine colon adenocarcinoma model MC38cea. MC38cea cells express the human carcinoembryonic antigen (CEA), allowing for infection with retargeted MV. Intratumoral application of MV-GMCSF significantly delayed tumor progression and prolonged median overall survival compared with control virus-treated mice. Importantly, more than one-third of mice treated with MV-GMCSF showed complete tumor remission and rejected successive tumor reengraftment, demonstrating robust long-term protection. An enhanced cell-mediated tumor-specific immune response could be detected by lactate dehydrogenase assay and interferon-γ enzyme-linked immunospot assay. Furthermore, MV-GMCSF treatment correlated with increased abundance of tumor-infiltrating CD3+lymphocytes analyzed by quantitative microscopy of tumor sections. These findings underline the potential of oncolytic, GM-CSF-expressing MV as an effective therapeutic cancer vaccine actively recruiting adaptive immune responses for enhanced therapeutic impact and tumor elimination. Thus, the treatment benefit of this combined immunovirotherapy approach has direct implications for future clinical trials

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BMC Bioinformatics >> Computational genetic neuroanatomy of the developing mouse brain: dimensionality reduction, visualization, and clustering

The structured organization of cells in the brain plays a key role in its functional efficiency.
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Zombie Simulation at Boy Scout Jamboree: Bioinformatics At Work

Zombie Simulation at Boy Scout Jamboree: Bioinformatics At Work | Virology and Bioinformatics from Virology.ca | Scoop.it
The Virginia Bioinformatics Institute's booth at this year's Boy Scout Jamboree teaches kids about the spread of infectious disease via a zombie virus app.
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Giant Pandoravirus is 1,000 times larger than influenca virus and contains 2556 genes

Giant Pandoravirus is 1,000 times larger than influenca virus and contains 2556 genes | Virology and Bioinformatics from Virology.ca | Scoop.it

Giant viruses turn out to be everywhere. It was the very giant-ness of giant viruses that allowed them to be overlooked for so long. Scientists first discovered viruses in the late 1800s when they were puzzled by a disease that beset tobacco plants. They mashed up wilted tobacco leaves with water and passed the mixture through fine porcelain filters that trapped bacteria and fungi. The clear liquid could still make healthy tobacco leaves sick. The Dutch botanist Martinus Beijerinck dubbed it “a contagious living fluid.”

 

In the 1930s, the invention of powerful microscopes finally allowed scientists to see viruses. They found that viruses were unlike ordinary cells: they didn’t generate their own fuel; they didn’t grow or divide. Instead, viruses invaded cells, hijacking their biochemistry to make new copies of themselves. Being small and simple seemed like part of the viral way of life, allowing them to replicate fast.

 

It wasn’t until 2003 that a team of French researchers discovered the first giant virus. They had been puzzling over sphere-shaped objects that were the size of bacteria but contained no bacterial DNA. Eventually they realized that they were looking at a monstrously oversized virus, containing 979 genes, much less than the newly discovered Pandoravirus.

 

Those first giant viruses were isolated from amoebae living in water from a cooling tower. Once scientists realized that viruses could be so large, they changed their search parameters and started finding other species in all manner of places, from swamps to rivers to contact lens fluid.

 

And along the way the biggest viruses got bigger. In 2011, Dr. Claverie and his colleagues set a new record with megaviruses, a type of giant virus with 1,120 genes they discovered in sea water off the coast of Chile. They then dug into the sediment below that sea water and discovered pandoravirsues, with more than twice as many genes.

 

Dr. Claverie speculates that pandoraviruses and other giant viruses evolved from free-living microbes that branched off from other life several billion years ago. “The type of cells they may have evolved from may have disappeared,” he said.

 

The idea that giant viruses represent separate branches on the tree of life is a controversial one that many other experts aren’t ready to embrace. “They provide no evidence for that notion, so it seems a distraction to me,” said T. Martin Embley, a professor of evolutionary molecular biology at Newcastle University.

 

Despite those reservations, Dr. Embley and other researchers hail pandoraviruses as an important discovery. “I think it’s wonderful that such crazy and divergent lifeforms continue to be discovered,” said Tom Williams, Dr. Embley’s colleague at Newcastle University.

 

The new study also drives home the fact that giant viruses are far from rare. Shortly after discovering pandoraviruses in sea floor sediment, Dr. Claverie and his colleagues found them in water from a lake in Australia, 10,000 miles away. “It definitely indicates that they must not be rare at all,” said Dr. Claverie.

 

Giant viruses may be so common, in fact, that they may be hiding inside of us, too. In a paper published online on July 2 in The Journal of Infectious Diseases, French researchers offered evidence that giant viruses dwell in healthy people. They isolated a new giant virus from blood donated by a healthy volunteer, and then found antibodies and other signs of the virus in four other donors.

 

Giant viruses may lurk harmlessly in our bodies, invading the amoebae we harbor. Whether they can make us sick is an open question. “I don’t believe we have the proof at the moment that these viruses could infect humans,” said Dr. Claverie.


Via Dr. Stefan Gruenwald
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Tomas Moravec's comment, July 23, 2013 4:14 AM
It is surprising how these large gyus avoided discovery for such a long time.
Ed Rybicki's comment, July 23, 2013 4:17 AM
Well, if they look like bacteria, and we are still finding new exemplars of those...
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Influenza: Pathways to human adaptation

Influenza: Pathways to human adaptation | Virology and Bioinformatics from Virology.ca | Scoop.it

An outbreak of avian H7N9 influenza in humans was reported in early 2013. Structural and infection studies are helping to reveal how these viruses can adapt to infect, and potentially transmit in, new species.

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Empty decoys divert antibodies from neutralizing gene therapy in cell, animal studies

Gene therapy researchers have produced a bioengineered decoy that fools the immune system and prevents it from mistakenly defeating the benefits delivered by a corrective gene.
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The wheat powdery mildew genome shows the unique evolution of an obligate biotroph

The wheat powdery mildew genome shows the unique evolution of an obligate biotroph | Virology and Bioinformatics from Virology.ca | Scoop.it
Thomas Wicker and colleagues report the whole-genome sequencing of four wheat powdery mildew (Blumeria graminis forma specialis tritici) isolates from different geographic regions.
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H5N1: Adenoviruses: Another cross-species threat

H5N1: Adenoviruses: Another cross-species threat | Virology and Bioinformatics from Virology.ca | Scoop.it
Thanks to Jeffery Norris for sending the link to this report in PLOS ONE: Experimental Cross-Species Infection of Common Marmosets by Titi Monkey Adenovirus.
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Heartland virus: One more reason to avoid ticks

Heartland virus: One more reason to avoid ticks | Virology and Bioinformatics from Virology.ca | Scoop.it
Ticks also transmit Lyme disease, a malaria-like disease, and a virus that seems to trigger meat allergies.
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A Mouse Model for Human Norovirus

ABSTRACT

Human noroviruses (HuNoVs) cause significant morbidity and mortality worldwide. However, despite substantial efforts, a small-animal model for HuNoV has not been described to date. Since “humanized” mice have been successfully used to study human-tropic pathogens in the past, we challenged BALB/c mice deficient in recombination activation gene (Rag) 1 or 2 and common gamma chain (γc) (Rag-γc) engrafted with human CD34+ hematopoietic stem cells, nonengrafted siblings, and immunocompetent wild-type controls with pooled stool isolates from patients positive for HuNoV. Surprisingly, both humanized and nonhumanized BALB/c Rag-γc-deficient mice supported replication of a GII.4 strain of HuNoV, as indicated by increased viral loads over input. In contrast, immunocompetent wild-type BALB/c mice were not infected. An intraperitoneal route of infection and the BALB/c genetic background were important for facilitating a subclinical HuNoV infection of Rag-γc-deficient mice. Expression of structural and nonstructural proteins was detected in cells with macrophage-like morphology in the spleens and livers of BALB/c Rag-γc-deficient mice, confirming the ability of HuNoV to replicate in a mouse model. In summary, HuNoV replication in BALB/c Rag-γc-deficient mice is dependent on the immune-deficient status of the host but not on the presence of human immune cells and provides the first genetically manipulable small-animal model for studying HuNoV infection.

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The Footprint of Genome Architecture in the Largest Genome Expansion in RNA Viruses

The Footprint of Genome Architecture in the Largest Genome Expansion in RNA Viruses | Virology and Bioinformatics from Virology.ca | Scoop.it

The small size of RNA virus genomes (2-to-32 kb) has been attributed to high mutation rates during replication, which is thought to lack proof-reading. This paradigm is being revisited owing to the discovery of a 3′-to-5′ exoribonuclease (ExoN) in nidoviruses, a monophyletic group of positive-stranded RNA viruses with a conserved genome architecture.

 

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MicroRNA-145 regulates oncolytic herpes simplex virus-1 for selective killing of human non-small cell lung cancer cells

MicroRNA-145 regulates oncolytic herpes simplex virus-1 for selective killing of human non-small cell lung cancer cells | Virology and Bioinformatics from Virology.ca | Scoop.it
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide, and novel treatment modalities to improve the prognosis of patients with advanced disease are highly desirable.
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Artificial microRNA-mediated resistance against the monopartite begomovirus Cotton leaf curl Burewala virus

Artificial microRNA-mediated resistance against the monopartite begomovirus Cotton leaf curl Burewala virus | Virology and Bioinformatics from Virology.ca | Scoop.it
Background

Cotton leaf curl disease, caused by single-stranded DNA viruses of the genus Begomovirus (family Geminiviridae), is a major constraint to cotton cultivation across Pakistan and north-western India. At this time only cotton varieties with moderate tolerance are available to counter the disease. microRNAs (miRNAs) are a class of endogenous small RNA molecules that play an important role in plant development, signal transduction, and response to biotic and a biotic stress. Studies have shown that miRNAs can be engineered to alter their target specificity. Such artificial miRNAs (amiRNAs) have been shown to provide resistance against plant-infecting viruses.

Results

Two amiRNA constructs, based on the sequence of cotton miRNA169a, were produced containing 21 nt of the V2 gene sequence of Cotton leaf curl Burewala virus (CLCuBuV) and transformed into Nicotiana benthamiana. The first amiRNA construct (P1C) maintained the miR169a sequence with the exception of the replaced 21 nt whereas in the second (P1D) the sequence of the miRNA169a backbone was altered to restore some of the hydrogen bonding of the mature miRNA duplex. P1C transgenic plants showed good resistance when challenge with CLCuBV; plants being asymptomatic with low viral DNA levels. The resistance to heterologous viruses was lower and correlated with the numbers of sequence mismatches between the amiRNA and the V2 gene sequence. P1D plants showed overall poorer resistance to challenge with all viruses tested.

Conclusions

The results show that the amiRNA approach can deliver efficient resistance in plants against a monopartite begomoviruses and that this has the potential to be broad-spectrum, providing protection from a number of viruses. Additionally the findings indicate that the levels of resistance depend upon the levels of complementarity between the amiRNA and the target sequence and the sequence of the miRNA backbone, consistent with earlier studies.

 

Geminivirus graphic courtesy of Russell Kightley Media

Ed Rybicki's insight:

Always nice to see some seriously cool technology being used in a developing country agricultural setting!  Nice one, NIBGE folks!

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Bioterrorism: A Dirty Little Threat With Huge Potential Consequences

Bioterrorism: A Dirty Little Threat With Huge Potential Consequences | Virology and Bioinformatics from Virology.ca | Scoop.it
All information for this article is taken from unclassified material. Most has been provided by a medical doctor and biomedical scientist who has an unconventional warfare background and prefers to be unnamed.
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BMC Bioinformatics >> Classification of protein motifs based on subcellular localization uncovers evolutionary relationships at both sequence and functional levels

Most proteins have evolved in specific cellular compartments that limit their functions and potential interactions.
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Solution to Vaccine Mystery Starts to Crystallize

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More than 80 years ago, manufacturers started spiking vaccines with alum, an additive, termed an adjuvant, that spurs a stronger reaction from the immune system. Yet scientists have struggled to explain exactly how alum, a catch-all term for several types of aluminum-containing adjuvants, does this. Recently, researchers have floated at least three possible mechanisms, including one that involves DNA spilled from dying cells. The reason alum works so well, several studies suggest, is that it trips an alarm that alerts the immune system when cells are in trouble. Insights into how alum works might allow researchers to design replacements that retain alum's advantages but lose some of its shortcomings.

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MERS Virus Not Yet a Global Emergency, WHO Panel Says - ScienceInsider

MERS Virus Not Yet a Global Emergency, WHO Panel Says - ScienceInsider | Virology and Bioinformatics from Virology.ca | Scoop.it

A special panel established by the World Health Organization (WHO) decided today that the novel coronavirus that has been infecting people in the Middle East is "very concerning," but does not yet constitute a "public health emergency of international concern." The new pathogen, known as Middle East respiratory syndrome (MERS) virus, has sickened 82 people and killed 45 of them so far.

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Dual virus-receptor duel

Dual virus-receptor duel | Virology and Bioinformatics from Virology.ca | Scoop.it
A study of two viruses that bind to the same cell surface receptor protein reveals how a cellular protein can change to prevent infection without affecting its role in the cell.
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PLOS Pathogens: Mutated and Bacteriophage T4 Nanoparticle Arrayed F1-V Immunogens from Yersinia pestis as Next Generation Plague Vaccines

PLOS Pathogens: Mutated and Bacteriophage T4 Nanoparticle Arrayed F1-V Immunogens from Yersinia pestis as Next Generation Plague Vaccines | Virology and Bioinformatics from Virology.ca | Scoop.it
Abstract

Pneumonic plague is a highly virulent infectious disease with 100% mortality rate, and its causative organism Yersinia pestis poses a serious threat for deliberate use as a bioterror agent. Currently, there is no FDA approved vaccine against plague. The polymeric bacterial capsular protein F1, a key component of the currently tested bivalent subunit vaccine consisting, in addition, of low calcium response V antigen, has high propensity to aggregate, thus affecting its purification and vaccine efficacy. We used two basic approaches, structure-based immunogen design and phage T4 nanoparticle delivery, to construct new plague vaccines that provided complete protection against pneumonic plague...

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