Viruses and Bioinformatics from Virology.uvic.ca
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Viruses and Bioinformatics from Virology.uvic.ca
Virus and bioinformatics articles with some microbiology and immunology thrown in for good measure
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PLOS Computational Biology: Inferring the Source of Transmission with Phylogenetic Data

PLOS Computational Biology: Inferring the Source of Transmission with Phylogenetic Data | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
Abstract

Identifying the source of transmission using pathogen genetic data is complicated by numerous biological, immunological, and behavioral factors. A large source of error arises when there is incomplete or sparse sampling of cases. Unsampled cases may act as either a common source of infection or as an intermediary in a transmission chain for hosts infected with genetically similar pathogens. It is difficult to quantify the probability of common source or intermediate transmission events, which has made it difficult to develop statistical tests to either confirm or deny putative transmission pairs with genetic data. We present a method to incorporate additional information about an infectious disease epidemic, such as incidence and prevalence of infection over time, to inform estimates of the probability that one sampled host is the direct source of infection of another host in a pathogen gene genealogy. These methods enable forensic applications, such as source-case attribution, for infectious disease epidemics with incomplete sampling, which is usually the case for high-morbidity community-acquired pathogens like HIV, Influenza and Dengue virus..."

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A novel splicing outcome reveals more than 2000 new mammalian protein isoforms

A novel splicing outcome reveals more than 2000 new mammalian protein isoforms | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it

We have recently characterized an instance of alternative splicing that differs from the canonical gene transcript by deletion of a length of sequence not divisible by three, but where translation can be rescued by an alternative start codon. This results in a predicted protein in which the amino terminus differs markedly in sequence from the known protein product(s), as it is translated from an alternative reading frame. Automated pipelines have annotated thousands of splice variants but have overlooked these protein isoforms, leading to them being underrepresented in current databases.

Results: Here we describe 1849 human and 733 mouse transcripts that can be transcribed from an alternate ATG. Of these, >80% have not been annotated previously. Those conserved between human and mouse genomes (and hence under likely evolutionary selection) are identified. We provide mass spectroscopy evidence for translation of selected transcripts. Of the described splice variants, only one has previously been studied in detail and converted the encoded protein from an activator of cell-function to a suppressor, demonstrating that these splice variants can result in profound functional change. We investigate the potential functional effects of this splicing using a variety of bioinformatic tools. The 2582 variants we describe are involved in a wide variety of biological processes, and therefore open many new avenues of research.

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Genomics, Medicine, and Pseudoscience: The top 6 vitamins and supplements you shouldn’t take

Genomics, Medicine, and Pseudoscience: The top 6 vitamins and supplements you shouldn’t take | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
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India has been free of polio for three years

India has been free of polio for three years | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
Three years ago today, on 13 January 2011, the last case of poliomyelitis was reported in India. Being polio-free is cause for celebration, but not for complacency.
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Parvovirus-Induced Depletion of Cyclin B1 Prevents Mitotic Entry of Infected Cells

Parvovirus-Induced Depletion of Cyclin B1 Prevents Mitotic Entry of Infected Cells | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
From molecules to physiology
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H7N9 has mutated, may spread from human to human: expert | Society | FOCUS TAIWAN - CNA ENGLISH NEWS

Shanghai, Jan. 11 (CNA) Chinese researchers have discovered mutations in the new strain of avian influenza A, known as H7N9, and have found that the virus has the ability to spread from human to human, the latest issue of China's Southern...
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Ed Rybicki's curator insight, January 13, 2014 5:09 AM

And so it begins...hopefully, NOT!

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PLOS Pathogens: Targeted Cytotoxic Therapy Kills Persisting HIV Infected Cells During ART

PLOS Pathogens: Targeted Cytotoxic Therapy Kills Persisting HIV Infected Cells During ART | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it

Antiretroviral therapy (ART) can reduce HIV levels in plasma to undetectable levels, but rather little is known about the effects of ART outside of the peripheral blood regarding persistent virus production in tissue reservoirs. Understanding the dynamics of ART-induced reductions in viral RNA (vRNA) levels throughout the body is important for the development of strategies to eradicate infectious HIV from patients. Essential to a successful eradication therapy is a component capable of killing persisting HIV infected cells during ART. Therefore, we determined the in vivo efficacy of a targeted cytotoxic therapy to kill infected cells that persist despite long-term ART. For this purpose, we first characterized the impact of ART on HIV RNA levels in multiple organs of bone marrow-liver-thymus (BLT) humanized mice and found that antiretroviral drug penetration and activity was sufficient to reduce, but not eliminate, HIV production in each tissue tested. For targeted cytotoxic killing of these persistent vRNA+ cells, we treated BLT mice undergoing ART with an HIV-specific immunotoxin. We found that compared to ART alone, this agent profoundly depleted productively infected cells systemically. These results offer proof-of-concept that targeted cytotoxic therapies can be effective components of HIV eradication strategies.

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Elephant shark genome provides unique insights into gnathostome evolution : Nature : Nature Publishing Group

Elephant shark genome provides unique insights into gnathostome evolution : Nature : Nature Publishing Group | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
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Multiple microRNAs targeted to internal ribosome entry site against foot-and-mouth disease virus infection in vitro and in vivo

Foot-and-mouth disease virus (FMDV) causes a severe vesicular disease in domestic and wild cloven-hoofed animals.
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Characterization of influenza vaccine immunogenicity using influenza antigen microarrays. [PLoS One. 2013]

AbstractBACKGROUND:

Existing methods to measure influenza vaccine immunogenicity prohibit detailed analysis of epitope determinants recognized by immunoglobulins. The development of highly multiplex proteomics platforms capable of capturing a high level of antibody binding information will enable researchers and clinicians to generate rapid and meaningful readouts of influenza-specific antibody reactivity.

METHODS:

We developed influenza hemagglutinin (HA) whole-protein and peptide microarrays and validated that the arrays allow detection of specific antibody reactivity across a broad dynamic range using commercially available antibodies targeted to linear and conformational HA epitopes. We derived serum from blood draws taken from 76 young and elderly subjects immediately before and 28±7 days post-vaccination with the 2008/2009 trivalent influenza vaccine and determined the antibody reactivity of these sera to influenza array antigens.

RESULTS:

Using linear regression and correcting for multiple hypothesis testing by the Benjamini and Hochberg method of permutations over 1000 resamplings, we identified antibody reactivity to influenza whole-protein and peptide array features that correlated significantly with age, H1N1, and B-strain post-vaccine titer as assessed through a standard microneutralization assay (p<0.05, q <0.2). Notably, we identified several peptide epitopes that were inversely correlated with regard to age and seasonal H1N1 and B-strain neutralization titer (p<0.05, q <0.2), implicating reactivity to these epitopes in age-related defects in response to H1N1 influenza. We also employed multivariate linear regression with cross-validation to build models based on age and pre-vaccine peptide reactivity that predicted vaccine-induced neutralization of seasonal H1N1 and H3N2 influenza strains with a high level of accuracy (84.7% and 74.0%, respectively).

CONCLUSION:

Our methods provide powerful tools for rapid and accurate measurement of broad antibody-based immune responses to influenza, and may be useful in measuring response to other vaccines and infectious agents.

  
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3D Virus Model Could Lead to Cure for Common Cold

3D Virus Model Could Lead to Cure for Common Cold | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it

A cure for the common cold may be just around the corner.

A three-dimensional model of the rhinovirus C, the virus behind up to half of all childhood colds, reveals why effective treatment for the ailment remains elusive and could open the door to a cure.

Researchers at the University of Wisconsin-Madisoncreated a meticulous topographical model, of the virus, which was only discovered in 2006. The model showed the virus is distinct from other cold viruses.


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Ed Rybicki's curator insight, November 3, 2013 10:12 AM

Yah, sure: every time a 3-D model is made, it's going to result in a vaccine.  Sure!  NOT!  But it's nice work

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Why vaccination matters, and why hippies and conspiracy theorists who say otherwise are dangerous

Why vaccination matters, and why hippies and conspiracy theorists who say otherwise are dangerous | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
Two things I'd like to bring to your attention today. One, Al Jazeera reports that hundreds of children have died in Pakistan as a result of a measles outbreak.

Via Ed Rybicki
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H1N1 flu surge in B.C. Lower Mainland lands people in ICUs

The chief medical officer for Fraser Health said Sunday that at least 20 people are in intensive care, some on ventilators, because of the H1N1 flu virus.
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Gold nanoparticles help develop new method for tracking viruses | Academy Of Finland

Gold nanoparticles help develop new method for tracking viruses | Academy Of Finland | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
Researchers at the Nanoscience Center (NSC) of the University of Jyväskylä in Finland have developed a novel method for the study of enterovirus structures and their functions. The method will help in obtaining new information on virus traffi...
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The Business of Running a Lab

The Business of Running a Lab | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
This week's post is a bit off-topic for everydaybiochemistry. Normally we talk about the biochemistry behind common activities, processes, foods, etc. We are still going to learn how something work...
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BMC Bioinformatics | Abstract | Skylign: a tool for creating informative, interactive logos representing sequence alignments and profile hidden Markov models

Logos are commonly used in molecular biology to provide a compact graphical representation of the conservation pattern of a set of sequences.
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Targeted Cytotoxic Therapy Kills Persisting HIV Infected Cells During ART

Targeted Cytotoxic Therapy Kills Persisting HIV Infected Cells During ART | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
From molecules to physiology
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Structural basis for hijacking CBF-β and CUL5 E3 ligase complex by HIV-1 Vif

The human immunodeficiency virus (HIV)-1 protein Vif has a central role in the neutralization of host innate defences by hijacking cellular proteasomal degradation pathways to subvert the antiviral activity of host restriction factors1, 2, 3, 4, 5, 6; however, the underlying mechanism by which Vif achieves this remains unclear. Here we report a crystal structure of the Vif–CBF-β–CUL5–ELOB–ELOC complex. The structure reveals that Vif, by means of two domains, organizes formation of the pentameric complex by interacting with CBF-β, CUL5 and ELOC. The larger domain (α/β domain) of Vif binds to the same side of CBF-β as RUNX1, indicating that Vif and RUNX1 are exclusive for CBF-β binding. Interactions of the smaller domain (α-domain) of Vif with ELOC and CUL5 are cooperative and mimic those of SOCS2 with the latter two proteins. A unique zinc-finger motif of Vif, which is located between the two Vif domains, makes no contacts with the other proteins but stabilizes the conformation of the α-domain, which may be important for Vif–CUL5 interaction. Together, our data reveal the structural basis for Vif hijacking of the CBF-β and CUL5 E3 ligase complex, laying a foundation for rational design of novel anti-HIV drugs.

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PLOS Pathogens: Cell Tropism Predicts Long-term Nucleotide Substitution Rates of Mammalian RNA Viruses

PLOS Pathogens: Cell Tropism Predicts Long-term Nucleotide Substitution Rates of Mammalian RNA Viruses | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it

Abstract

The high rates of RNA virus evolution are generally attributed to replication with error-prone RNA-dependent RNA polymerases. However, these long-term nucleotide substitution rates span three orders of magnitude and do not correlate well with mutation rates or selection pressures. This substitution rate variation may be explained by differences in virus ecology or intrinsic genomic properties. We generated nucleotide substitution rate estimates for mammalian RNA viruses and compiled comparable published rates, yielding a dataset of 118 substitution rates of structural genes from 51 different species, as well as 40 rates of non-structural genes from 28 species. Through ANCOVA analyses, we evaluated the relationships between these rates and four ecological factors: target cell, transmission route, host range, infection duration; and three genomic properties: genome length, genome sense, genome segmentation. Of these seven factors, we found target cells to be the only significant predictors of viral substitution rates, with tropisms for epithelial cells or neurons (P<0.0001) as the most significant predictors. Further, one-tailed t-tests showed that viruses primarily infecting epithelial cells evolve significantly faster than neurotropic viruses (P<0.0001 and P<0.001 for the structural genes and non-structural genes, respectively). These results provide strong evidence that the fastest evolving mammalian RNA viruses infect cells with the highest turnover rates: the highly proliferative epithelial cells. Estimated viral generation times suggest that epithelial-infecting viruses replicate more quickly than viruses with different cell tropisms. Our results indicate that cell tropism is a key factor in viral evolvability.

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A Unique and Conserved Neutralization Epitope in H5N1 Influenza Viruses Identified by an Antibody against the A/Goose/Guangdong/1/96 Hemagglutinin

Despite substantial efforts to control and contain H5N1 influenza viruses, bird flu viruses continue to spread and evolve. Neutralizing antibodies against conserved epitopes on the viral hemagglutinin (HA) could confer immunity to the diverse H5N1 virus strains and provide information for effective vaccine design. Here, we report the characterization of a broadly neutralizing murine monoclonal antibody, H5M9, to most H5N1 clades and subclades that was elicited by immunization with viral HA of A/Goose/Guangdong/1/96 (H5N1), the immediate precursor of the current dominant strains of H5N1 viruses. The crystal structures of the Fab′ fragment of H5M9 in complexes with H5 HAs of A/Vietnam/1203/2004 and A/Goose/Guangdong/1/96 reveal a conserved epitope in the HA1 vestigial esterase subdomain that is some distance from the receptor binding site and partially overlaps antigenic site C of H3 HA. Further epitope characterization by selection of escape mutants and epitope mapping by flow cytometry analysis of site-directed mutagenesis of HA with a yeast cell surface display identified four residues that are critical for H5M9 binding. D53, Y274, E83a, and N276 are all conserved in H5N1 HAs and are not in H5 epitopes identified by other mouse or human antibodies. Antibody H5M9 is effective in protection of H5N1 virus both prophylactically and therapeutically and appears to neutralize by blocking both virus receptor binding and postattachment steps. Thus, the H5M9 epitope identified here should provide valuable insights into H5N1 vaccine design and improvement, as well as antibody-based therapies for treatment of H5N1 infection.

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Recognition of Errors in the Refinement and Validation of Three Begomovirus AC1s

Recognition of Errors in the Refinement and Validation of Three Begomovirus AC1s | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
Geminiviruses were recognized in 1978 by the International Committee on the Taxonomy of viruses on the basis of their unique virion morphology and possession of ssDNA as their genomic material [1, 2].
Ed Rybicki's insight:

Sounds like a good application of public resource!

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ClassyFlu: Classification of Influenza A Viruses with Discriminatively Trained Profile-HMMs - PLOS ONE

ClassyFlu: Classification of Influenza A Viruses with Discriminatively Trained Profile-HMMs - PLOS ONE | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it

Accurate and rapid characterization of influenza A virus (IAV) hemagglutinin (HA) and neuraminidase (NA) sequences with respect to subtype and clade is at the basis of extended diagnostic services and implicit to molecular epidemiologic studies. ClassyFlu is a new tool and web service for the classification of IAV sequences of the HA and NA gene into subtypes and phylogenetic clades using discriminatively trained profile hidden Markov models (HMMs), one for each subtype or clade. ClassyFlu merely requires as input unaligned, full-length or partial HA or NA DNA sequences. It enables rapid and highly accurate assignment of HA sequences to subtypes H1–H17 but particularly focusses on the finer grained assignment of sequences of highly pathogenic avian influenza viruses of subtype H5N1 according to the cladistics proposed by the H5N1 Evolution Working Group. NA sequences are classified into subtypes N1–N10. ClassyFlu was compared to semiautomatic classification approaches using BLAST and phylogenetics and additionally for H5 sequences to the new “Highly Pathogenic H5N1 Clade Classification Tool” (IRD-CT) proposed by the Influenza Research Database. Our results show that both web tools (ClassyFlu and IRD-CT), although based on different methods, are nearly equivalent in performance and both are more accurate and faster than semiautomatic classification. A retraining of ClassyFlu to altered cladistics as well as an extension of ClassyFlu to other IAV genome segments or fragments thereof is undemanding. This is exemplified by unambiguous assignment to a distinct cluster within subtype H7 of sequences of H7N9 viruses which emerged in China early in 2013 and caused more than 130 human infections. http://bioinf.uni-greifswald.de/ClassyFlu is a free web service. For local execution, the ClassyFlu source code in PERL is freely available.

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Endangered Tigers, Lion and Red Pandas died due to Canine Distemper Virus: Scientists

Endangered Tigers, Lion and Red Pandas died due to Canine Distemper Virus: Scientists | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it
Endangered animals are perishing due to infection caused by canine distemper virus (CDV) Endangered animals are perishing due to infection caused by canine distemper virus (CDV)

About Canine distemper Virus

• CDV is a common disease in domestic dogs.

• CDV affects different systems of the body including nervous and respiratory system in these animals.

• CDV breaks down the immunity system and causes various secondary bacterial infections, which leads to death.

• It spreads in the animals that eat dogs infected with the virus and/or drink water from same source.

- See more at: http://www.jagranjosh.com/current-affairs/endangered-tigers-lion-and-red-pandas-died-due-to-canine-distemper-virus-scientists-1388994254-1#sthash.nAQd6k4r.dpuf

 

Paramyxovirus particle courtesy of Linda Stannard


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#Lyme Disease: Call for a “Manhattan Project” to Combat the Epidemic

#Lyme Disease: Call for a “Manhattan Project” to Combat the Epidemic | Viruses and Bioinformatics from Virology.uvic.ca | Scoop.it

Lyme disease is the most common tick-borne illness in the world today. Until recently, the Centers for Disease Control and Prevention (CDC) reported an average of only 30,000 cases of Lyme disease per year in the United States. Three preliminary CDC studies, however, have indicated that the true incidence of Lyme disease may be greater than 300,000 cases and as high as one million cases per year in the United States. A majority of these cases occur in women and children. Based on this new information, Lyme disease should be recognized as a virulent epidemic that is at least six times more common than HIV/AIDS. In response to these alarming statistics, we review the ongoing problems with diagnosis and treatment of Lyme disease. We propose the need for an HIV/AIDS-style “Manhattan project” to combat this serious epidemic that threatens the physical and mental health of millions of people around the world.

 

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