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PLOS Computational Biology: The Roots of Bioinformatics in ISMB

PLOS Computational Biology: The Roots of Bioinformatics in ISMB | Virology and Bioinformatics from Virology.ca | Scoop.it
PLOS Computational Biology is an open-access
Nicolas Palopoli's insight:

Besides the interesting recall of the Intelligent Systems for Molecular Biology (ISMB) annual conferences on computational biology, it offers a nice insight into current state-of-the-art methodologies and upcoming trends in the discipline.

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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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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.


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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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Occurrence and reassortment of avian influenza A (H7N9) viruses derived from coinfected birds in China

Over the course of two waves of infection, H7N9 avian influenza A virus has caused 436 human infections and claimed 170 lives in China as of July 2014. To investigate the prevalence and genetic diversity of H7N9 we surveyed avian influenza viruses in poultry in Jiangsu province within the outbreak epicenter. We found frequent occurrence of H7N9/H9N2 co-infection in chickens. Molecular clock phylogenetic analysis confirms co-infection by H7N9/H9N2 viruses and also reveals that the identity of the H7N9 outbreak lineage is confounded by ongoing reassortment between outbreak viruses and diverse H9N2 viruses in domestic birds. Experimental inoculation of a co-infected sample in cell culture yielded two reassortant H7N9 strains with polymerase segments from the original H9N2 strain. Ongoing reassortment between the H7N9 outbreak lineage and diverse H9N2 viruses may generate new strains with the potential to infect humans, highlighting the need for continued viral surveillance in poultry and humans.

Importance We found frequent occurrence of H7N9/H9N2 co-infection in chickens. The H7N9 outbreak lineage is confounded by ongoing reassortment between H7N9 and H9N2 viruses. The importance of H9N2 viruses as the source of novel avian influenza virus infections in humans requires continuous attention.

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How to bury your academic writing

How to bury your academic writing | Virology and Bioinformatics from Virology.ca | Scoop.it
Book chapters can allow freedom to think about your work in line with broader theoretical issues, but if you're tempted to write a book chapter for an edited collection, it might be best to reconsi...
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Ebola - WakaWaka

Ebola - WakaWaka | Virology and Bioinformatics from Virology.ca | Scoop.it
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Marburgvirus Resurgence in Kitaka Mine Bat Population after Extermination Attempts

Marburgvirus Resurgence in Kitaka Mine Bat Population after Extermination Attempts | Virology and Bioinformatics from Virology.ca | Scoop.it

Marburg virus (MARV) and Ravn virus (RAVV), collectively called marburgviruses, cause Marburg hemorrhagic fever (MHF) in humans. In July 2007, 4 cases of MHF (1 fatal) occurred in miners at Kitaka Mine in southern Uganda. Later, MHF occurred in 2 tourists who visited Python Cave, ≈50 km from Kitaka Mine. One of the tourists was from the United States (December 2007) and 1 was from the Netherlands (July 2008); 1 case was fatal (1,2,3). The cave and the mine each contained 40,000–100,000 Rousettus aegyptiacus bats (Egyptian fruit bats).

Longitudinal investigations of the outbreaks at both locations were initiated by the Viral Special Pathogens Branch of the Centers for Disease Control and Prevention (CDC, Atlanta, GA, USA, and Entebbe, Uganda) in collaboration with the Uganda Wildlife Authority (UWA) and the Uganda Virus Research Institute (UVRI). During these studies, genetically diverse MARVs and RAVVs were isolated directly from bat tissues, and infection levels of the 2 viruses were found to increase in juvenile bats on a predictable bi-annual basis (4,5). However, investigations at Kitaka Mine were stopped when the miners exterminated the bat colony by restricting egress from the cave with papyrus reed barriers and then entangling the bats in fishing nets draped over the exits. The trapping continued for weeks, and the entrances were then sealed with sticks and plastic. These depopulation efforts were documented by researchers from UVRI, the CDC, the National Institute of Communicable Diseases (Sandringham, South Africa), and UWA during site visits to Kitaka Mine (Technical Appendix[PDF - 124 KB - 1 page] Figure). In August 2008, thousands of dead bats were found piled in the forest, and by November 2008, there was no evidence of bats living in the mine; whether 100% extermination was achieved is unknown. CDC, UVRI, and UWA recommended against extermination, believing that any results would be temporary and that such efforts could exacerbate the problem if bat exclusion methods were not complete and permanent (6,7).

 

Ed Rybicki's insight:

So there's the bats' revenge: exterminate us, and we'll come back with a higher prevalence - with more diverse viruses!

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SearchSmallRNA: a graphical interface tool for the assemblage of viral genomes using small RNA libraries data - Virology Journal

SearchSmallRNA: a graphical interface tool for the assemblage of viral genomes using small RNA libraries data - Virology Journal | Virology and Bioinformatics from Virology.ca | Scoop.it
Next-generation parallel sequencing (NGS) allows the identification of viral pathogens by sequencing the small RNAs of infected hosts. Thus, viral genomes may be assembled from host immune response products without prior virus enrichment, amplification or purification. However, mapping of the vast information obtained presents a bioinformatics challenge.
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Ten Simple Rules for Better Figures

Ten Simple Rules for Better Figures | Virology and Bioinformatics from Virology.ca | Scoop.it

"Scientific visualization is classically defined as the process of graphically displaying scientific data. However, this process is far from direct or automatic. There are so many different ways to represent the same data: scatter plots, linear plots, bar plots, and pie charts, to name just a few. Furthermore, the same data, using the same type of plot, may be perceived very differently depending on who is looking at the figure. A more accurate definition for scientific visualization would be a graphical interface between people and data. In this short article, we do not pretend to explain everything about this interface; rather, see [1], [2] for introductory work. Instead we aim to provide a basic set of rules to improve figure design and to explain some of the common pitfalls."

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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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Basics of the Unix Philosophy

Chris Upton + helpers's insight:

The ‘Unix philosophy’ originated with Ken Thompson's early meditations on how to design a small but capable operating system with a clean service interface. It grew as the Unix culture learned things about how to get maximum leverage out of Thompson's design. It absorbed lessons from many sources along the way.

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Genetically Modified Mosquitoes Pave the Way for Dengue Fever Prevention | Viruses101 | Learn Science at Scitable

Genetically Modified Mosquitoes Pave the Way for Dengue Fever Prevention | Viruses101 | Learn Science at Scitable | Virology and Bioinformatics from Virology.ca | Scoop.it
Over 40% of the word's population is at risk of contracting Dengue Fever, a mosquito borne virus. Scientists are now using genetically modified mosquitoes to try and prevent the spread of Dengue Fever.
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▶ Jonathan Yewdell - How to Succeed in Science - YouTube

Jonathan Yewdell M.D., Ph.D. (NIH) -- leading immunologist and head of NIAID Cell Biology and Viral Immunology -- delivers a grantsmanship lecture on "How to...
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Filoviruses Require Endosomal Cysteine Proteases for Entry but Exhibit Distinct Protease Preferences

Ken Yaw Agyeman-Badu's insight:

Filoviruses are enveloped viruses that cause sporadic outbreaks of severe hemorrhagic fever [CDC, MMWR Morb. Mortal. Wkly. Rep. 50:73–77, 2001; Colebunders and Borchert, J. Infect. 40:16–20, 2000; Colebunders et al., J. Infect. Dis. 196(Suppl. 2):S148–S153, 2007; Geisbert and Jahrling, Nat. Med. 10:S110-S121, 2004]. Previous studies revealed that endosomal cysteine proteases are host factors for ebolavirus Zaire (Chandran et al., Science 308:1643–1645, 2005; Schornberg et al., J. Virol. 80:4174–4178, 2006). In this report, we show that infection mediated by glycoproteins from other phylogenetically diverse filoviruses are also dependent on these proteases and provide additional evidence indicating that they cleave GP1 and expose the binding domain for the critical host factor Niemann-Pick C1. Using selective inhibitors and knockout-derived cell lines, we show that the ebolaviruses Zaire and Cote d'Ivoire are strongly dependent on cathepsin B, while the ebolaviruses Sudan and Reston and Marburg virus are not. Taking advantage of previous studies of cathepsin B inhibitor-resistant viruses (Wong et al., J. Virol. 84:163–175, 2010), we found that virus-specific differences in the requirement for cathepsin B are correlated with sequence polymorphisms at residues 47 in GP1 and 584 in GP2. We applied these findings to the analysis of additional ebolavirus isolates and correctly predicted that the newly identified ebolavirus species Bundibugyo, containing D47 and I584, is cathepsin B dependent and that ebolavirus Zaire-1995, the single known isolate of ebolavirus Zaire that lacks D47, is not. We also obtained evidence for virus-specific differences in the role of cathepsin L, including cooperation with cathepsin B. These studies strongly suggest that the use of endosomal cysteine proteases as host factors for entry is a general property of members of the family Filoviridae.

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Ken Yaw Agyeman-Badu's curator insight, September 14, 11:22 PM

Filoviruses are enveloped viruses that cause sporadic outbreaks of severe hemorrhagic fever [CDC, MMWR Morb. Mortal. Wkly. Rep. 50:73–77, 2001; Colebunders and Borchert, J. Infect. 40:16–20, 2000; Colebunders et al., J. Infect. Dis. 196(Suppl. 2):S148–S153, 2007; Geisbert and Jahrling, Nat. Med. 10:S110-S121, 2004]. Previous studies revealed that endosomal cysteine proteases are host factors for ebolavirus Zaire (Chandran et al., Science 308:1643–1645, 2005; Schornberg et al., J. Virol. 80:4174–4178, 2006). In this report, we show that infection mediated by glycoproteins from other phylogenetically diverse filoviruses are also dependent on these proteases and provide additional evidence indicating that they cleave GP1 and expose the binding domain for the critical host factor Niemann-Pick C1. Using selective inhibitors and knockout-derived cell lines, we show that the ebolaviruses Zaire and Cote d'Ivoire are strongly dependent on cathepsin B, while the ebolaviruses Sudan and Reston and Marburg virus are not. Taking advantage of previous studies of cathepsin B inhibitor-resistant viruses (Wong et al., J. Virol. 84:163–175, 2010), we found that virus-specific differences in the requirement for cathepsin B are correlated with sequence polymorphisms at residues 47 in GP1 and 584 in GP2. We applied these findings to the analysis of additional ebolavirus isolates and correctly predicted that the newly identified ebolavirus species Bundibugyo, containing D47 and I584, is cathepsin B dependent and that ebolavirus Zaire-1995, the single known isolate of ebolavirus Zaire that lacks D47, is not. We also obtained evidence for virus-specific differences in the role of cathepsin L, including cooperation with cathepsin B. These studies strongly suggest that the use of endosomal cysteine proteases as host factors for entry is a general property of members of the family Filoviridae.

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PolyCTLDesigner: a computational tool for constructing polyepitope T-cell antigens - BMC Research Notes

Construction of artificial polyepitope antigens is one of the most promising strategies for developing more efficient and safer vaccines evoking T-cell immune responses. Epitope rearrangements and utilization of certain spacer sequences have been proven to greatly influence the immunogenicity of polyepitope constructs. However, despite numerous efforts towards constructing and evaluating artificial polyepitope immunogens as well as despite numerous computational methods elaborated to date for predicting T-cell epitopes, peptides binding to TAP and for antigen processing prediction, only a few computational tools were currently developed for rational design of polyepitope antigens.

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Chimpanzee adenovirus vaccine generates acute and durable protective immunity against ebolavirus challenge : Nature Medicine : Nature Publishing Group

A chimpanzee adenovirus-based vaccination approach elicits acute and long-term protection against ebolavirus challenge in nonhuman primates.

Via Mel Melendrez-Vallard
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