Viral Modeling and Simulation
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In Vivo Imaging of Influenza Virus Infection in Immunized Mice

Immunization is the cornerstone of seasonal influenza control and represents an important component of pandemic preparedness strategies. Using a bioluminescent reporter virus, we demonstrate the application of noninvasive in vivo imaging system (IVIS) technology to evaluate the preclinical efficacy of candidate vaccines and immunotherapy in a mouse model of influenza. Sequential imaging revealed distinct spatiotemporal kinetics of bioluminescence in groups of mice passively or actively immunized by various strategies that accelerated the clearance of the challenge virus at different rates and by distinct mechanisms. Imaging findings were consistent with conclusions derived from virus titers in the lungs and, notably, were more informative than conventional efficacy endpoints in some cases. Our findings demonstrate the reliability of IVIS as a qualitative approach to support preclinical evaluation of candidate medical countermeasures for influenza in mice.
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Computational virology: From the inside out

Computational virology: From the inside out | Viral Modeling and Simulation | Scoop.it
Viruses typically pack their genetic material within a protein capsid. Enveloped viruses also have an outer membrane made up of a lipid bilayer and membrane-spanning glycoproteins. X-ray diffraction and cryoelectron microscopy provide high resolutio
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[Prediction of selective inhibition of neuraminidase from various influenza virus strains by potential inhibitors]. - PubMed - NCBI

[Prediction of selective inhibition of neuraminidase from various influenza virus strains by potential inhibitors]. - PubMed - NCBI | Viral Modeling and Simulation | Scoop.it
Biomed Khim. 2016 Nov;62(6):691-703. doi: 10.18097/PBMC20166206691.
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Modelling Virus and Antibody Dynamics during Dengue Virus Infection Suggests a Role for Antibody in Virus Clearance

Modelling Virus and Antibody Dynamics during Dengue Virus Infection Suggests a Role for Antibody in Virus Clearance | Viral Modeling and Simulation | Scoop.it
Author Summary Dengue is a globally important viral disease. Despite this, there is still much unknown about the immunology, virology and epidemiology of dengue. As for all viral infections, the interaction between virus and immune response is a complex one. Using data collected from patients, we model how the virus replicates in an infected individual and how the human antibody response acts to control that replication. We show that the timing and magnitude of the growth and decline of virus and antibody levels in dengue-infected patients are consistent with antibody playing a key role in controlling infection. Our results are of use in the evaluation of potential antiviral drugs and vaccines.
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Structure of the immature Zika virus at 9 A resolution : Nature Structural & Molecular Biology : Nature Research

Structure of the immature Zika virus at 9 A resolution : Nature Structural & Molecular Biology : Nature Research | Viral Modeling and Simulation | Scoop.it
The cryo-EM structure of immature Zika virus shows partially ordered capsid proteins and reveals differences between pre-epidemic and epidemic strains at protein interfaces within the trimeric spikes.
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Ultra-deep sequencing of VHSV isolates contributes to understanding the role of viral quasispecies

Ultra-deep sequencing of VHSV isolates contributes to understanding the role of viral quasispecies | Viral Modeling and Simulation | Scoop.it
The high mutation rate of RNA viruses enables the generation of a genetically diverse viral population, termed a quasispecies, within a single infected host. This high in-host genetic diversity enables an RNA virus to adapt to a diverse array of selective pressures such as host immune response and switching between host species. The negative-sense, single-stranded RNA virus, viral haemorrhagic septicaemia virus (VHSV), was originally considered an epidemic virus of cultured rainbow trout in Europe, but was later proved to be endemic among a range of marine fish species in the Northern hemisphere. To better understand the nature of a virus quasispecies related to the evolutionary potential of VHSV, a deep-sequencing protocol specific to VHSV was established and applied to 4 VHSV isolates, 2 originating from rainbow trout and 2 from Atlantic herring. Each isolate was subjected to Illumina paired end shotgun sequencing after PCR amplification and the 11.1 kb genome was successfully sequenced with an average coverage of 0.5–1.9 × 106 sequenced copies. Differences in single nucleotide polymorphism (SNP) frequency were detected both within and between isolates, possibly related to their stage of adaptation to host species and host immune reactions. The N, M, P and Nv genes appeared nearly fixed, while genetic variation in the G and L genes demonstrated presence of diverse genetic populations particularly in two isolates. The results demonstrate that deep sequencing and analysis methodologies can be useful for future in vivo host adaption studies of VHSV.
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A review of bioinformatic pipeline frameworks

High-throughput bioinformatic analyses increasingly rely on pipeline frameworks to process sequence and metadata. Modern implementations of these frameworks differ on three key dimensions: using an implicit or explicit syntax, using a configuration, convention or class-based design paradigm and offering a command line or workbench interface. Here I sur- vey and compare the design philosophies of several current pipeline frameworks. I provide practical recommendations based on analysis requirements and the user base.

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Complete and Incomplete Genome Packaging of Influenza A and B Viruses

Complete and Incomplete Genome Packaging of Influenza A and B Viruses | Viral Modeling and Simulation | Scoop.it
The genomes of influenza A and B viruses comprise eight segmented, single-stranded, negative-sense viral RNAs (vRNAs). Although segmentation of the virus genome complicates the packaging of infectious progeny into virions, it provides an evolutionary benefit in that it allows viruses to exchange vRNAs with other strains. Influenza A viruses are believed to package their eight different vRNAs in a specific manner. However, several studies have shown that many viruses are noninfectious and fail to package at least one vRNA. Therefore, the genome-packaging mechanism is not fully understood. In this study, we used electron microscopy to count the number of ribonucleoproteins (RNPs) inside the virions of different influenza A and B virus strains. All eight strains examined displayed eight RNPs arranged in a “7+1” configuration in which a central RNP was surrounded by seven RNPs. Three-dimensional analysis of the virions showed that at least 80% of the virions packaged all eight RNPs; however, some virions packaged only five to seven RNPs, with the exact proportion depending on the strain examined. These results directly demonstrate that most viruses package eight RNPs, but some do indeed package fewer. Our findings support the selective genome-packaging model and demonstrate the variability in the number of RNPs incorporated by virions, suggesting that the genome-packaging mechanism of influenza viruses is more flexible than previously thought.


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Virus Explorer | HHMI BioInteractive

Virus Explorer | HHMI BioInteractive | Viral Modeling and Simulation | Scoop.it
RT @UpbmAsso: #virus en modèles #3D: influenza, HIV, rabies, zika, papillomavirus (HPV), Ebola
https://t.co/0ax3iAlfO7 https://t.co/OD99Ym…
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Infectio: a Generic Framework for Computational Simulation of Virus Transmission between Cells

Viruses spread between cells, tissues, and organisms by cell-free and cell-cell mechanisms, depending on the cell type, the nature of the virus, or the phase of the infection cycle. The mode of viral transmission has a large impact on disease development
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Influenza virus intracellular replication dynamics, release kinetics, and particle morphology during propagation in MDCK cells

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Labeling of virus components for advanced, quantitative imaging analyses. - PubMed - NCBI

FEBS Lett. 2016 Mar 14. doi: 10.1002/1873-3468.12131. [Epub ahead of print] REVIEW
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Towards a structural understanding of RNA synthesis by negative strand RNA viral polymerases

Towards a structural understanding of RNA synthesis by negative strand RNA viral polymerases | Viral Modeling and Simulation | Scoop.it

Highlights
• Crystal and cryo-EM structures of NSV polymerases influenza, La Crosse and VSV.
• Segmented and non-segmented NSV polymerases have a similar extended core architecture.
• Influenza and LACV structures show how the vRNA promoter is bound.
• The cap-snatching mechanism of influenza polymerase (sNSV) is explained.
• VSV (nsNSV) capping domains block product exit and thus need to rearrange.
• Separate exit channels for template and product allow replication within the RNP context.

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Virology Lectures 2017 #15: Mechanisms of Pathogenesis

One goal of virology research is to understand viral pathogenesis - how viruses cause disease. In this lecture we discuss animal models for studyin
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Viral Protein Kinetics of Piscine Orthoreovirus Infection in Atlantic Salmon Blood Cells. - PubMed - NCBI

Viral Protein Kinetics of Piscine Orthoreovirus Infection in Atlantic Salmon Blood Cells. - PubMed - NCBI | Viral Modeling and Simulation | Scoop.it
Viruses. 2017 Mar 18;9(3). pii: E49. doi: 10.3390/v9030049.
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Comparison and validation of two computational models of Chagas disease: A thirty year perspective from Venezuela.

Epidemics. 2017 Mar;18:81-91. doi: 10.1016/j.epidem.2017.02.004.
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Viral RNA Degradation and Diffusion Act as a Bottleneck for the Influenza A Virus Infection Efficiency

Viral RNA Degradation and Diffusion Act as a Bottleneck for the Influenza A Virus Infection Efficiency | Viral Modeling and Simulation | Scoop.it
Author Summary Influenza A virus carries its segmented genome inside a lipid envelope. Since genome replication occurs inside the nucleus, the main goal of virus infection is to deliver all genome segments through the cytoplasm into the nucleus. After endocytic uptake, influenza viruses transit early endosomal compartments and eventually reach late endosomes. Within a complex maturation process, the endosomal lumen acidifies while the vesicles are transported trough the cytosol. If and how these early processes affect virus infection remained mostly speculative. To reach a better understanding and to quantify the physical interplay between membrane fusion, genome diffusion and infection, we developed a mathematical model that comprises all initial steps of virus infection until genome delivery. We calibrated our model using experimental data and challenged its predictions using recombinant viruses to introduce perturbations. Our results provide a theoretical framework to understand the importance of the endosomal virus passage before membrane fusion and genome release. We further unraveled RNA degradation as a previously unknown limiting factor for virus infection. Our work will help to make predictions and evaluate newly occurring virus strains, regarding their infection efficiency in a given host cell, by simply considering their pH sensitivity.
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The virome: a missing component of biological interaction networks in health and disease

The virome: a missing component of biological interaction networks in health and disease | Viral Modeling and Simulation | Scoop.it
Host-associated viral populations, viromes, have been understudied relative to their contribution to human physiology. Viruses interact with host gene networks, influencing both health and disease. Analysis of host gene networks in the absence of virome analysis risks missing important network information.
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Scientists watch an immune system fight the flu in real time

Scientists watch an immune system fight the flu in real time | Viral Modeling and Simulation | Scoop.it
To date, biologists have typically had to study the progress of a virus through indirect means, such as studying the antibodies -- actually tracking th

Via Marcelo de Carvalho Bittencourt, Kenzibit
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Gilbert C FAURE's curator insight, October 1, 2016 12:44 PM
By using multiphoton microscopy in tandem with a laser and fluorescence, the team monitored influenza virus in a mouse's trachea (where the transluency made imaging possible) through the infection and immune system response.
already posted on mucosal immunity
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Single-Molecule FISH Reveals Non-selective Packaging of Rift Valley Fever Virus Genome Segments

Author Summary The bunyavirus family is one of the largest virus families on Earth, of which several members cause severe disease in humans, animals or plants. Little is known about the mechanisms that facilitate the production of infectious bunyavirus virions, which should contain at least one copy of the small (S), medium (M) and large (L) genome segment. In this study, we investigated the genome packaging process of the Rift Valley fever virus (RVFV) by visualizing individual genome segments inside infected cells and virions. Experiments performed with wild-type virus, two- and four-segmented variants, and a variant with a codon-shuffled M segment showed that the production of infectious virions is a non-selective process and is unlikely to involve the formation of a supramolecular viral RNA complex. These observations have broad implications for understanding the bunyavirus replication cycle and may facilitate the development of new vaccines and the identification of novel antiviral targets.
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T cells bully influenza virus into submission | Virology News

Australian researchers are at the forefront of developing a vaccine which could lead to lifelong immunity against the influenza virus. | Virology News
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Dissecting Virus Infectious Cycles by Cryo-Electron Microscopy

In response to events such as receptor binding and endocytic triggers, viruses undergo large-scale, dynamic conformational changes necessary for cell entry and genome delivery. In later stages of the infectious cycle, replication machinery must read and synthesize nucleic acid strands to generate new copies of genetic material, and structural proteins must assemble and package the appropriate contents in order to produce new infectious particles. Structural elucidation of these events is key to understanding them and their inhibition by antiviral agents such as neutralizing antibodies and drugs. Electron microscopy is a versatile technique that offers the ability to resolve three-dimensional structures of individual viral proteins and whole virions in multiple functional states, even in cells at different stages of infection (Fig 1). Here we focus on the use of transmission electron microscopy of frozen-hydrated specimens, i.e., cryo-electron microscopy (cryo-EM). A major advantage of cryo-EM over other structural approaches is that samples of a broad range of sizes can be imaged under near-physiological conditions with native hydration intact. This approach does not require the specimen to be fixed, stained, or coaxed into a crystalline lattice. This versatility has enabled cryo-EM to expand the envelope of structural virology and opened new avenues for understanding the molecular and cellular processes of virus infection and pathogenesis.


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Time-Resolved Imaging of Single HIV-1 Uncoating In Vitro and in Living Cells

Author Summary HIV-1 genome and key enzymes required for establishing productive infection are encased in a cone-shaped shell made of the capsid protein (CA). After being released into the cytosol of target cells, the cone-shaped core complex undergoes a series of carefully orchestrated steps, including uncoating (loss of CA). HIV-1 uncoating remains poorly understood, due in part to the lack of direct assays enabling studies of this process in living cells. Here, we introduce a novel strategy for labeling the HIV-1 capsid without genetically modifying the CA protein. We designed a novel fluorescent cyclophilin A construct that binds the capsid with an extremely high avidity and (1) efficiently incorporates into virions without compromising infectivity; (2) remains bound to cores after viral fusion; and (3) is lost from post-fusion cores along with CA. The novel imaging assay provides new insights into the kinetics and spatial distribution of HIV-1 uncoating in living cells.
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