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Evidence for Antigenic Seniority in Influenza A (H3N2) Antibody Responses in Southern China

Evidence for Antigenic Seniority in Influenza A (H3N2) Antibody Responses in Southern China | Virology and Bioinformatics from Virology.ca | Scoop.it

"A key observation about the human immune response to repeated exposure to influenza A is that the first strain infecting an individual apparently produces the strongest adaptive immune response. Although antibody titers measure that response, the interpretation of titers to multiple strains – from the same sera – in terms of infection history is clouded by age effects, cross reactivity and immune waning. From July to September 2009, we collected serum samples from 151 residents of Guangdong Province, China, 7 to 81 years of age. Neutralization tests were performed against strains representing six antigenic clusters of H3N2 influenza circulating between 1968 and 2008, and three recent locally circulating strains. Patterns of neutralization titers were compared based on age at time of testing and age at time of the first isolation of each virus. Neutralization titers were highest for H3N2 strains that circulated in an individual's first decade of life (peaking at 7 years). Further, across strains and ages at testing, statistical models strongly supported a pattern of titers declining smoothly with age at the time a strain was first isolated. Those born 10 or more years after a strain emerged generally had undetectable neutralization titers to that strain (<1:10). Among those over 60 at time of testing, titers tended to increase with age. The observed pattern in H3N2 neutralization titers can be characterized as one of antigenic seniority: repeated exposure and the immune response combine to produce antibody titers that are higher to more ‘senior’ strains encountered earlier in life."

 

An interesting paper, which helps explain several observations made over the years with pandemic flu: for example, in the 2009 H1N1 pandemic, older people seemed to be more protected - and the same was probably true of the 1918 pandemic.

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Virology and Bioinformatics from Virology.ca
Virus and bioinformatics articles with some microbiology and immunology thrown in for good measure
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It's a group effort - the curators:

It's a group effort - the curators: | Virology and Bioinformatics from Virology.ca | Scoop.it

get in touch if you want to help curate this topic

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Op-Ed: Ebola is everybody’s business

Op-Ed: Ebola is everybody’s business | Virology and Bioinformatics from Virology.ca | Scoop.it

The images are beamed around the world. Emaciated bodies, lying solo at hospital gates, in one-bedroom corrugated iron shantytown shacks, in bare makeshift hospital rooms or on potholed, muddy streets.  Poor people are dying in mostly undignified settings, often alone, often shunned by fearful family and friends or an absent health system. The lucky few who reach humanitarian centres have a chance to survive, but it is mostly against great and often insurmountable odds. And sadly, even if many people do make it to some form of help, they are failed because there simply is no health system able to offer the basic level of healthcare, to which every single human being in the world should be entitled to access as a human right.

As was the case for many years with HIV, those who have the means and money to buy a hospital bed where they can access clean water, some medication, caring and trained healthcare workers or a basic intravenous drip, have a chance of survival or at the very least a dignified and pain-free end. However for thousands of west Africans contracting Ebola has been a painful, debilitating and undignified death sentence.

In many ways the ever-growing Ebola epidemic is showing up the fault lines, not only in buckling or collapsed health systems, but in society’s failure to show solidarity with the “them”, with the poor and voiceless.

The 2014 Ebola outbreak needs to become a moment where those who follow will mark it as a turning point where the world rallied; where donors, rich countries and health agencies acted decisively to invest in health systems on which billions of vulnerable people rely, but are failed daily.

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Absolutely!

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PLEK: a tool for predicting long non-coding RNAs and messenger RNAs based on an improved k-mer scheme

High-throughput transcriptome sequencing (RNA-seq) technology promises to discover novel protein-coding and non-coding transcripts, particularly the identification of long non-coding RNAs (lncRNAs) from de novo sequencing data. This requires tools that are not restricted by prior gene annotations, genomic sequences and high-quality sequencing.
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Myxoma virus oncolytic efficiency can be enhanced

Myxoma virus oncolytic efficiency can be enhanced | Virology and Bioinformatics from Virology.ca | Scoop.it

Myxoma virus (MYXV) is one of many animal viruses that exhibit oncolytic properties in transformed human cells. Compared to orthopoxviruses like vaccinia (VACV), MYXV spreads inefficiently, which could compromise its use in treating tumors and their associated metastases. 

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The Scale of the Universe - An Interactive Visual Understanding of How Small Viruses and Microorganisms Really Are

Zoom from the edge of the universe to the quantum foam of spacetime and learn about everything in between.
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CorMut: an R/Bioconductor package for computing correlated mutations based on selection pressure

Summary: Correlated mutations constitute a fundamental idea in evolutionary biology, and understanding correlated mutations will, in turn, facilitate an understanding of the genetic mechanisms governing evolution. CorMut is an R package designed to compute correlated mutations in the unit of codon or amino acid mutation. Three classical methods were incorporated, and the computation results can be represented as correlation mutation networks. CorMut also enables the comparison of correlated mutations between two different evolutionary conditions.

Availability and implementation: CorMut is released under the GNU General Public License within bioconductor project, and freely available athttp://bioconductor.org/packages/release/bioc/html/CorMut.html.

Contact: mal@chinaaids.cn or yshao08@gmail.com

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BioFlow: a web based workflow management software for design and execution of genomics pipelines

Bioinformatics data analysis is usually done sequentially by chaining together multiple tools. These are created by writing scripts and tracking the inputs and outputs of all stages. Writing such scripts require programming skills. Executing multiple pipelines in parallel and keeping track of all the generated files is difficult and error prone. Checking results and task completion requires users to remotely login to their servers and run commands to identify process status. Users would benefit from a web-based tool that allows creation and execution of pipelines remotely. The tool should also keep track of all the files generated and maintain a history of user activities.
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Identification of Nucleotide-Level Changes Impacting Gene Content and Genome Evolution in Orthopoxviruses.

Poxviruses are composed of large dsDNA genomes coding for several hundred genes whose variation has supported virus adaptation to a wide variety of hosts over their long evolutionary history. Comparative genomics has suggested that the Orthopoxvirus genus in particular has undergone reductive evolution, with the most recent common ancestor likely possessing a gene complement consisting of all genes present in any existing modern-day orthopoxvirus species, similar to the current Cowpox virus species. As orthopoxviruses adapt to new environments, the selection pressure on individual genes may be altered, driving sequence divergence and possible loss of function. This is evidenced by accumulation of mutations and loss of protein-coding open reading frames (ORFs) that progress from individual missense mutations, to gene truncation through the introduction of early stop mutations (ESMs), gene fragmentation, and in some cases, a total loss of the ORF. In this study, we have constructed a whole-genome alignment for representative isolates from each Orthopoxvirusspecies and used it to identify the nucleotide-level changes that have led to gene content variation. By identifying the changes that have led to ESMs, we were able to determine that short indels were the major cause of gene truncations, and that the genome length is proportional to the number of ESMs present. We also identified the number and types of protein functional motifs still present in truncated genes to assess their functional significance.

IMPORTANCE This work contributes to our understanding of reductive evolution in poxviruses by identifying genomic remnants such as SNPs and indels left behind by evolutionary processes. Our comprehensive analysis of the genomic changes leading to gene truncation and fragmentation was able to detect some of the remnants of these evolutionary processes still present in orthopoxvirus genomes, and suggest that these viruses are under continual adaptation due to changes in their environment. These results further our understanding of the evolutionary mechanisms that drive virus variation, allowing orthopoxviruses to adapt to particular environmental niches. Understanding the past evolutionary history of these virus pathogens may help predict their future evolutionary potential.

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Comparison of Transcriptional Profiles Between CD4+ and CD8+ T Cells in HIV Type 1-Infected Patients

The CD4+/CD8+ T cell ratio is altered when HIV-1 infects the human immune system. However, the exact mechanisms of how CD4+ and CD8+ T cells participate in HIV infection are still unknown. This study used bioinformatics methods to compare the transcriptional profiles between CD4+ and CD8+ T cells in HIV-1-infected patients in order to explore the potential molecular mechanisms of CD4+ and CD8+ T cells in HIV-1 infection. We found that expression patterns of differentially expressed genes (DEG) in CD4+ T cells were dramatically different from those in CD8+ T cells. We also constructed protein–protein interaction (PPI) networks to extract functional modules at each stage, and found that some of the important genes such as BRCA1 were central hubs of the modules. Finally, we applied functional annotation to the modules and found that CD4+/CD8+ T cells played critical roles in regulating the cell cycle and other cellular pathways. Thus, this study would greatly further our understanding of the roles of T cells in HIV infection, and provide potential clues for developing AIDS vaccines in the future.

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transphylo - Bayesian inference of infectious disease transmission from a phylogeny - Google Project Hosting

transphylo - Bayesian inference of infectious disease transmission from a phylogeny - Google Project Hosting | Virology and Bioinformatics from Virology.ca | Scoop.it

This is the homepage of TransPhylo, a software package for the Bayesian inference of infectious disease transmission from a phylogeny. The input is a dated phylogeny, where leaves correspond to pathogens isolated from the infected hosts. The main output is a transmission tree which indicates who infected whom. Such reconstruction can be achieved by colouring the branches of the phylogeny using a separate colour for each host, and such that the subtree coloured in a given colour represents the evolution happening within the corresponding host. Changes of colours on branches therefore correspond to transmission events from one host to another.

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Tangram: a comprehensive toolbox for mobile element insertion detection

Background:
Mobile elements (MEs) constitute greater than 50% of the human genome as a result of repeated insertion events during human genome evolution.

Via Mel Melendrez-Vallard
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Epstein-Barr Virus Cut Out Of Infected Human Cells By CRISPR-Cas9 Genome Editing

Epstein-Barr Virus Cut Out Of Infected Human Cells By CRISPR-Cas9 Genome Editing | Virology and Bioinformatics from Virology.ca | Scoop.it

Researchers at Stanford exploited the newly developed precision gene editing technology known CRISPR-Cas9 into an anti-virus technology by cutting out Epstein-Barr virus from the host genome of infected cells.  Infected cells successfully treated this way scale back proliferation caused by viral programs and engage in a self-destruct program known as “apoptosis”, or controlled cell death.  EBV is known to express a “brake” protein that suppresses apoptosis, a way to evade natural defense mechanisms.  The researchers also show importantly that there was no toxic effect on non-infected cells.

 

Epstein-Barr virus (EBV) is most often associated with mononucleosis but is also a cause of more serious conditions such as Burkitt’s lymphoma, nasopharyngeal cancer, and even autoimmune diseases.   No therapy exists but the CRISPR-Cas9 study is a valuable avenue as it overcomes two challenges posed by the virus.

 

The first challenge is during the latent stage of its life cycle it integrates into the genome and exhibits few targets for intervention. In fact most therapeutics under development are focused on attacking the virus during its active “lytic” stage so are not expected to work for cells with virus in latent stage.  In the latent stage the virus is still “on”, running a latency program that prompts the cell to proliferate.

 

The second challenge is that the virus encodes and expresses with the help of the host cell a “brake” protein BHRF1that stops the self-destruct signal stimulated by immune cells in effort to rid the body of cells that have become compromised.   The “brake” signal is one reason why EBV is frequently found in cancers: under normal conditions cells that start off on the path to cancer by acquiring mutations get stopped by the cell’s natural ability to undergo “programmed cell death” but EBV halts this process.

 

The technology for CRISPR-Cas9 entails two parts.  The first is the “cutting” enzyme, which is able to cut out pieces of viral DNA that has integrated into the host genome.  The second is a “guide RNA” which is a nucleic acid template that matches the desired target, in this case parts of the EBV sequence.  The researchers designed a CRISPR-Cas9 system that targets EBV based on its sequence in computer databases.

 

Once the cells were treated the researches found that latently infected cells no longer proliferated.  To ensure that this was not a toxic effect of treatment, the same CRISPR-Cas9 system was applied to cells that lack EBV, in which case there was no effect on proliferation.  This is an important point as some criticize CRISPR-Cas9 for its off-target effects in which unintentional cutting occurs.


Via Dr. Stefan Gruenwald
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Human H7N9 and H5N1 influenza viruses differ in induction of cytokines and tissue tropism

Since emerging in 2013, the avian-origin H7N9 influenza viruses have resulted in over 400 human infections leading to 115 deaths to date. Although the epidemiology differs from human highly pathogenic avian H5N1 influenza infections, there is a similar rapid progression to acute respiratory distress syndrome (ARDS). The aim of these studies was to compare the pathological and immunological characteristics of a panel of human H7N9 and H5N1 viruses in vitro and in vivo. Although there were similarities between particular H5N1 and H7N9 viruses, including association between lethal disease and spread to the alveolar spaces and kidney, there were also strain-specific differences. Both H5N1 and H7N9 viruses are capable of causing lethal infections, with mortality correlating most strongly with wider distribution of viral antigen in the lungs, rather than with traditional measures of viral titer and host responses. Strain-specific differences included hypercytokinemia in H5N1 infections that was not seen with the H7N9 infections regardless of lethality. Conversely, H7N9 viruses showed a greater tropism for respiratory epithelium covering nasal passages and NALT than H5N1 viruses, which may explain the enhanced transmission in ferret models. Overall these studies highlight some distinctive properties of H5N1 and H7N9 viruses in different in vitro and in vivo models.

Importance The novel avian-origin H7N9 pandemic represents a serious threat to public health. The ability of H7N9 to cause serious lung pathology leading in some cases to the development of acute respiratory distress syndrome is of particular concern. Initial reports of H7N9 infection compared them to infections caused by highly pathogenic avian (HPAI) H5N1 viruses. Thus, it is of critical importance to understand the pathology and immunological response to infection with H7N9 as compared to HPAI H5N1 viruses. We compared these responses in both in vitro and in vivo models, and found that H5N1 and H7N9 infections exhibit distinct pathological, immunological and tissue tropism differences that could explain differences in clinical disease and viral transmission.

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“History of Microbiology” | Microbiology with Educator.com

History of Microbiology” | Microbiology with Educator.com ▻Watch more at http://educator.com/biology/microbiology/carpenter/ Understand your Microbiology homework and ace the test...
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Effect of Formaldehyde Inactivation on Poliovirus

Inactivated polio vaccines, which have been used in many countries for more than 50 years, are produced by treating live poliovirus (PV) with formaldehyde. However, the molecular mechanisms underlying virus inactivation are not well understood. Infection by PV is initiated by virus binding to specific cell receptors, which results in viral particles undergoing sequential conformational changes that generate altered structural forms (135S and 80S particles) and leads to virus cell entry. We have analyzed the ability of inactivated PV to bind to the human poliovirus receptor (hPVR) using various techniques such as ultracentrifugation, fluorescence-activated cell sorting flow cytometry and real-time reverse transcription-PCR (RT-PCR). The results showed that although retaining the ability to bind to hPVR, inactivated PV bound less efficiently in comparison to live PV. We also found that inactivated PV showed resistance to structural conversion in vitro, as judged by measuring changes in antigenicity, the ability to bind to hPVR, and viral RNA release at high temperature. Furthermore, viral RNA from inactivated PV was shown to be modified, since cDNA yields obtained by RT-PCR amplification were severely reduced and no infectious virus was recovered after RNA transfection into susceptible cells.

 

Ed Rybicki's insight:

People have been treating poliovirus with formaldehyde for over 60 years - and it's only NOW that someone thought to study in detail what happens!

 

I love this stuff: analytical centrifugation could have been done any time in the last fifty years (and has been, in determining structural transitions) but the newer techniques such as flow cytometry and RT-PCR could not. Analytically determining now what was empirically observed to work when polio vaccines were first made, is a historically important vindication of pioneering work that has almost made the viruses go away.

 

Simple and obvious findings, essentially - it is obvious that methylene bridging between amino acids would affect structural transitions; so too that HCHO treatment would kill viral ssRNA - but it hadn't been DONE properly previously.  Great stuff!

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The evolution of pandemic influenza: evidence from India, 1918-19

The 1918-19 'Spanish' Influenza was the most devastating pandemic in recent history, with estimates of global mortality ranging from 20 to 50 million. The focal point of the pandemic was India, with an estimated death toll of between 10 and 20 million. We will characterize the pattern of spread, mortality, and evolution of the 1918 influenza across India using spatial or temporal data.
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Will the Ebola virus go airborne? (And is that even the right question?)

Will the Ebola virus go airborne? (And is that even the right question?) | Virology and Bioinformatics from Virology.ca | Scoop.it
The virus spreads through contact with bodily fluids. What if that changes?
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Virus Variation Resource pages for Ebolavirus, MERS coronoavirus give quick and easy access to related sequences and other data

Virus Variation Resource pages for Ebolavirus, MERS coronoavirus give quick and easy access to related sequences and other data | Virology and Bioinformatics from Virology.ca | Scoop.it
NCBI has created resource pages for Ebolavirus and MERS coronavirus, giving users an easy way to find all sequences related to these pathogens. These pages aggregate links to virus data at NCBI and also provide important links out to other information at the CDC, WHO, and HealthMap.
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Conserved and host-specific features of influenza virion architecture

Conserved and host-specific features of influenza virion architecture | Virology and Bioinformatics from Virology.ca | Scoop.it

Viruses use virions to spread between hosts, and virion composition is therefore the primary determinant of viral transmissibility and immunogenicity. However, the virions of many viruses are complex and pleomorphic, making them difficult to analyse in detail. Here we address this by identifying and quantifying virion proteins with mass spectrometry, producing a complete and quantified model of the hundreds of host-encoded and viral proteins that make up the pleomorphic virions of influenza viruses. We show that a conserved influenza virion architecture is maintained across diverse combinations of virus and host. This ‘core’ architecture, which includes substantial quantities of host proteins as well as the viral protein NS1, is elaborated with abundant host-dependent features. As a result, influenza virions produced by mammalian and avian hosts have distinct protein compositions. Finally, we note that influenza virions share an underlying protein composition with exosomes, suggesting that influenza virions form by subverting microvesicle production.

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OMICtools: an informative directory for multi-omic data analysis

Recent advances in ‘omic’ technologies have created unprecedented opportunities for biological research, but current software and database resources are extremely fragmented. OMICtools is a manually curated metadatabase that provides an overview of more than 4400 web-accessible tools related to genomics, transcriptomics, proteomics and metabolomics. All tools have been classified by omic technologies (next-generation sequencing, microarray, mass spectrometry and nuclear magnetic resonance) associated with published evaluations of tool performance. Information about each tool is derived either from a diverse set of developers, the scientific literature or from spontaneous submissions. OMICtools is expected to serve as a useful didactic resource not only for bioinformaticians but also for experimental researchers and clinicians.

Database URL: http://omictools.com/

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Virulence-Affecting Amino Acid Changes in the PA Protein of H7N9 Influenza A Viruses

Novel avian-origin influenza A(H7N9) viruses were first reported to infect humans in March 2013. To date, 143 human cases, including 45 deaths, have been recorded. By using sequence comparisons and phylogenetic and ancestral inference analyses, we identified several distinct amino acids in the A(H7N9) polymerase PA protein, some of which may be mammalian adapting. Mutant viruses possessing some of these amino acid changes, singly or in combination, were assessed for their polymerase activities and growth kinetics in mammalian and avian cells and for their virulence in mice. We identified several mutants that were slightly more virulent in mice than the wild-type A(H7N9) virus, A/Anhui/1/2013. These mutants also exhibited increased polymerase activity in human cells but not in avian cells. Our findings indicate that the PA protein of A(H7N9) viruses has several amino acid substitutions that are attenuating in mammals.

 

IMPORTANCE Novel avian-origin influenza A(H7N9) viruses emerged in the spring of 2013. By using computational analyses of A(H7N9) viral sequences, we identified several amino acid changes in the polymerase PA protein, which we then assessed for their effects on viral replication in cultured cells and mice. We found that the PA proteins of A(H7N9) viruses possess

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Forty reasons why we need animals in research

Understanding Animal Research provides information about animal research and testing and the resulting advances in science and medicine.
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Virus Control Goes Epigenetic

Virus Control Goes Epigenetic | Virology and Bioinformatics from Virology.ca | Scoop.it
From molecules to physiology
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Ebola: While Big Pharma Slept

Ebola: While Big Pharma Slept | Virology and Bioinformatics from Virology.ca | Scoop.it
The story of Ebola's most recent (and now deadliest) outbreak is a book worthy topic.

Via Ed Rybicki
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U.S. Military to Send 3,000 to Battle Ebola Virus

U.S. Military to Send 3,000 to Battle Ebola Virus | Virology and Bioinformatics from Virology.ca | Scoop.it
The U.S. military will deploy about 3,000 personnel to West Africa to coordinate international aid, build treatment centers and train health-care workers as part of President Barack Obama's offensive against a worsening Ebola outbreak, a senior...

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TLR5-Mediated Sensing of Gut Microbiota Is Necessary for Antibody Responses to Seasonal Influenza Vaccination: Immunity

Systems biological analysis of immunity to the trivalent inactivated influenza vaccine (TIV) in humans revealed a correlation between early expression of TLR5 and the magnitude of the antibody response. Vaccination of Trl5−/− mice resulted in reduced antibody titers and lower frequencies of plasma cells, demonstrating a role for TLR5 in immunity to TIV. This was due to a failure to sense host microbiota. Thus, antibody responses in germ-free or antibiotic-treated mice were impaired, but restored by oral reconstitution with a flagellated, but not aflagellated, strain of E. coli. TLR5-mediated sensing of flagellin promoted plasma cell differentiation directly and by stimulating lymph node macrophages to produce plasma cell growth factors. Finally, TLR5-mediated sensing of the microbiota also impacted antibody responses to the inactivated polio vaccine, but not to adjuvanted vaccines or the live-attenuated yellow fever vaccine. These results reveal an unappreciated role for gut microbiota in promoting immunity to vaccination.

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