Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1085292 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Infection with a single influenza A virus (IAV) is only rarely sufficient to initiate productive infection. Here, we exploit both single cell approaches and whole-animal systems to show that the extent of IAV reliance on multiple infection varies with virus strain and host species. Influenza A/guinea fowl/HK/WF10/99 (H9N2) [GFHK99] virus exhibits strong dependence on collective interactions in mammalian systems. This reliance focuses viral progeny production within coinfected cells and therefore results in frequent genetic exchange through reassortment. In contrast, GFHK99 virus has greatly reduced dependence on multiple infection in avian systems, indicating a role for host factors in viral collective interactions. Genetic mapping implicated the viral polymerase as a major driver of multiple infection dependence. Mechanistically, quantification of incomplete viral genomes showed that their complementation only partly accounts for the observed reliance on coinfection. Indeed, even when all polymerase components are detected in single cell mRNA sequencing, robust polymerase activity of GFHK99 virus in mammalian cells is reliant on multiple infection. In sum, IAV collective interactions not only augment reassortment, but can also overcome species-specific barriers to infection. These findings underscore the importance of virus-virus interactions in IAV infection, evolution and emergence. We used a single-cell sequencing platform (10x Genomics) to elucidate the differential infection rate of an avian influenza A virus on an avian cell line (DF1) and a mammalian (MDCK) cell line. Our work on IAV reassortment has raised new questions about the fundamental strategies that drive influenza virus evolution. Our data indicate that a large majority of influenza virus genomesare incomplete within cells, comprising less than the eight complete segments normally found in a replication competent infectious viral particle. This led us to ask: what underlying mechanisms give rise to incomplete genomes? What constitute an infectious unit? What are the implications for viral diversification, evolution and spread. By addressing these questions, we will advance he field by deepening our understanding how viral infections are initiated and propagated.
2020-06-16 | GSE135553 | GEO
Project description:While a common symptom of influenza and coronavirus disease 2019 (COVID-19) is fever, its physiological role on host resistance to viral infection remains less clear. Here, we demonstrate that exposure of mice to the high ambient temperature of 36 °C increase host resistance to viral pathogens including influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). High heat-exposed mice increase basal body temperature over 38 °C to enable more bile acids production in a gut microbiota-dependent manner. The gut microbiota-derived deoxycholic acid (DCA) and its plasma membrane-bound receptor Takeda G-protein-coupled receptor 5 (TGR5) signaling increase host resistance to influenza virus infection by suppressing virus replication and neutrophil-dependent tissue damage. Furthermore, the DCA and its nuclear farnesoid X receptor (FXR) agonist protect Syrian hamster from lethal SARS-CoV-2 infection. Moreover, we demonstrate that certain bile acids are reduced in the plasma of COVID-19 patients who developed moderate I/II disease compared with minor illness group. These findings uncover an unexpected mechanism by which virus-induced high fever increases host resistance to influenza virus and SARS-CoV-2 in a gut microbiota-dependent manner.
2023-02-14 | ST002479 | MetabolomicsWorkbench
Project description:While a common symptom of influenza and coronavirus disease 2019 (COVID-19) is fever, its physiological role on host resistance to viral infection remains less clear. Here, we demonstrate that exposure of mice to the high ambient temperature of 36 °C increase host resistance to viral pathogens including influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). High heat-exposed mice increase basal body temperature over 38 °C to enable more bile acids production in a gut microbiota-dependent manner. The gut microbiota-derived deoxycholic acid (DCA) and its plasma membrane-bound receptor Takeda G-protein-coupled receptor 5 (TGR5) signaling increase host resistance to influenza virus infection by suppressing virus replication and neutrophil-dependent tissue damage. Furthermore, the DCA and its nuclear farnesoid X receptor (FXR) agonist protect Syrian hamster from lethal SARS-CoV-2 infection. Moreover, we demonstrate that certain bile acids are reduced in the plasma of COVID-19 patients who developed moderate I/II disease compared with minor illness group. These findings uncover an unexpected mechanism by which virus-induced high fever increases host resistance to influenza virus and SARS-CoV-2 in a gut microbiota-dependent manner.
2023-01-24 | ST002476 | MetabolomicsWorkbench
Project description:Predicting and constraining RNA virus evolution require understanding the molecular factors that define the mutational landscape accessible to these pathogens. RNA viruses typically have high mutation rates, resulting in frequent production of protein variants with compromised biophysical properties. Their evolution is necessarily constrained by the consequent challenge to protein folding and function. We hypothesize that host proteostasis mechanisms, may be significant determinants of the fitness of viral protein variants, serving as a critical force shaping viral evolution. Here, we test this hypothesis by propagating influenza in host cells displaying chemically-controlled, divergent proteostasis environments. We find that both the nature of selection on the influenza genome and the accessibility of specific mutational trajectories are significantly impacted by host proteostasis. These findings provide new insights into features of host–pathogen interactions that shape viral evolution, and into the potential design of host proteostasis-targeted antiviral therapeutics that are refractory to resistance.
2017-11-15 | GSE102797 | GEO
Project description:Influenza A virus is a kind of single negative-stranded RNA virus which belongs to the Orthomyxoviridae family. It can cause localized outbreak or worldwide epidemic in a short time for its great contagiosity, fast spread speed and a wide range of host, and H1N1 influenza virus is a strong pathogenic subtype of influenza A virus. Influenza A virus infection has been shown to alter miRNA expression both in cultured cells and in animal models. We used microRNA microarrays to detail the programme of microRNA expression and identified distinct classes of differentially regulated microRNAs during this process.
2014-10-21 | GSE62495 | GEO
Project description:Himanshu Manchanda, Nora Seidel, Andi Krumbholz, Andreas Sauerbrei, Michaela Schmidtke & Reinhard Guthke. Within-host influenza dynamics: a small-scale mathematical modeling approach. Biosystems 118 (2014).
The emergence of new influenza viruses like the pandemic H1N1 influenza A virus in 2009 (A(H1N1)pdm09) with unpredictable difficulties in vaccine coverage and established antiviral treatment protocols emphasizes the need of new murine models to prove the activity of novel antiviral compounds in vivo. The aim of the present study was to develop a small-scale mathematical model based on easily attainable experimental data to explain differences in influenza kinetics induced by different virus strains in mice. To develop a three-dimensional ordinary differential equation model of influenza dynamics, the following variables were included: (i) viral pathogenicity (P), (ii) antiviral immune defense (D), and (iii) inflammation due to pro-inflammatory response (I). Influenza virus-induced symptoms (clinical score S) in mice provided the basis for calculations of P and I. Both, mono- and biphasic course of mild to severe influenza induced by three clinical A(H1N1)pdm09 strains and one European swine H1N2 virus were comparatively and quantitatively studied by fitting the mathematical model to the experimental data. The model hypothesizes reasons for mild and severe influenza with mono- as well as biphasic course of disease. According to modeling results, the second peak of the biphasic course of infection is caused by inflammation. The parameters (i) maximum primary pathogenicity, (ii) viral infection rate, and (iii) rate of activation of the immune system represent most important parameters that quantitatively characterize the different pattern of virus-specific influenza kinetics.
2024-09-02 | BIOMD0000000712 | BioModels
Project description:We used the microarray data to analyze host cells response on A549 cells infected with Influenza A virus (A/Singapore/478/2009 (pH1N1)) The Influenza A virus (A/Singapore/478/2009 (pH1N1)) infected A549 cells were harvested at 2, 4, 6, 8 and 10 hpi and RNA extraction was performed using standard protocol as described by Affymetrix. The aim of this experiment is to analyze host response to Influenza A virus (A/Singapore/478/2009 (pH1N1)) infection.
2013-01-03 | E-GEOD-31518 | biostudies-arrayexpress
Project description:Dynamic nuclear SUMO modifications play essential roles in orchestrating cellular responses to proteotoxic stress, DNA damageand DNA virus infections. Here, we describe the host SUMOylation response to the nuclear-replicating RNA pathogen, influenz A virus. Using quantitative proteomics to compare SUMOylation responses to various stresses (including heat-shock), we reveal that influenza A virus infection causes unique re-targeting of SUMO1 and SUMO2 to a diverse range of host proteins involved in transcription, mRNA processing, RNA quality control and DNA damage repair. This global characterization of influenza virus-triggered SUMO remodeling provides a proteomic resource to understand host nuclear SUMOylation responses to infection.
2017-03-31 | MSV000080853 | MassIVE
Project description:Influenza A virus (IAV) lacks the enzyme for adding 5â caps to its RNAs, and thus snatches the 5â ends of host capped RNAs to prime transcription. Neither the preference of the host RNA sequences snatched, nor the effect of âcap-snatchingâ on host processes has been completely defined. Previous studies of influenza cap-snatching used poly(A)-selected RNA from infected cells or relied solely on annotated host protein-coding genes to define host mRNAs selected by the virus. To examine the substrate-product relationship between all host RNAs, including non-coding RNAs, and viral RNAs, we used an unbiased approach to identify the host and viral capped RNAs from IAV-infected cells. We demonstrate that IAV predominantly snatches caps from non-coding host RNAs, particularly U1 and U2 small nuclear RNAs (snRNAs). Because snRNAs regulate host mRNA processing, cap-snatching of snRNAs may constitute a means by which IAV hijacks host cell metabolism. examine caps snatched by influenza virus A
2015-11-23 | E-GEOD-67493 | biostudies-arrayexpress
Project description:Annually, influenza A viruses circulate the world causing wide-spread sickness, economic loss, and death. One way to better defend against influenza virus-induced disease may be to develop novel host-based therapies, targeted at mitigating viral pathogenesis through the management of virus-dysregulated host functions. However, mechanisms that govern aberrant host responses to influenza virus infection remain incompletely understood. We previously showed that the pandemic H1N1 virus influenza A/California/04/2009 (H1N1; CA04) has enhanced pathogenicity in the lungs of cynomolgus macaques relative to a seasonal influenza virus isolate (A/Kawasaki/UTK-4/2009 (H1N1; KUTK4)). Here, we used microarrays to identify host gene sequences that were highly differentially expressed (DE) in CA04-infected macaque lungs, and we employed a novel strategy – combining functional and pathway enrichment analyses, transcription factor binding site enrichment analysis and protein-protein interaction data – to create a CA04 differentially regulated host response network. This network describes enhanced viral RNA sensing, immune cell signaling and cell cycle arrest in CA04-infected lungs, and highlights a novel, putative role for the MYC-associated zinc finger (MAZ) transcription factor in regulating these processes.
2012-10-01 | GSE39018 | GEO