Single cell sequencing of resting and Influenza-stimulated mononcluear phagocytes of African and Europeans with varying degree of ex-vivo susceptibility to Influenza
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PROVIDER: EGAS00001005000 | EGA |
REPOSITORIES: EGA
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Project description:During viral infection, a large number of immune response signaling molecules including the interferon regulatory (IRF) family and type I interferon (IFN) transcribe. The exact identity and expression levels of fish IRFs and type-I IFNs during viral infection remains largely unknown. Here, we utilized Illumina sequencing technology to determine differential expression patterns for both zebrafish IRFs and type-I IFNs during two stages of SVCV infection, i.e. 6h and 24h post-infection. For 12 zebrafish IRFs, we identified DrIRF1 mRNA as one of the most abundant in normal tissues and also in SVCV-infected tissues, but DrIRF11 had a very weak basal expression and was almost not induced by SVCV infection. We also identified the highly basal expression of DrIRF7, which together with DrIRF3, was highly induced by SVCV infection. For type-I IFNs, zebrafish has four IFN genes, three of which, IFN1/2/3, particularly IFN 1 and IFN 3, were significantly transcribed under the same conditions.
2014-11-11 | GSE63133 | GEO
Project description:The host response to influenza A infections is strongly influenced by host genetic factors. Animal models of genetically diverse mouse strains are well suitable to identify host genes involved in severe pathology, viral replication and immune responses. Here, we have utilizing a dual RNAseq approach that allowed us to investigate both viral and host gene expression in the same individual from a single expression assay after H1N1 infection. We performed a comparative expression analysis to identify (i) correlations between host genes and the viral gene expression, (ii) host genes involved in viral replication, and (iii) genes showing differential expression between the two mouse strains after infection. These genes may be key players involved in regulating the differences in pathogenesis and host defense mechanisms after influenza A infections. Expression levels of influenza segments correlated well with the viral load and may thus be used as surrogates for conventional viral load measurements. Furthermore, we investigated the functional role of two genes, Reg3g and Irf7, in knock-out mice and found that deletion of the Irf7 gene renders the host highly susceptible to H1N1 infection.
2015-07-06 | GSE66040 | GEO
Project description:The host response to influenza A infections is strongly influenced by host genetic factors. Animal models of genetically diverse mouse strains are well suitable to identify host genes involved in severe pathology, viral replication and immune responses. Here, we have utilizing a dual RNAseq approach that allowed us to investigate both viral and host gene expression in the same individual from a single expression assay after H1N1 infection. We performed a comparative expression analysis to identify (i) correlations between host genes and the viral gene expression, (ii) host genes involved in viral replication, and (iii) genes showing differential expression between the two mouse strains after infection. These genes may be key players involved in regulating the differences in pathogenesis and host defense mechanisms after influenza A infections. Expression levels of influenza segments correlated well with the viral load and may thus be used as surrogates for conventional viral load measurements. Furthermore, we investigated the functional role of two genes, Reg3g and Irf7, in knock-out mice and found that deletion of the Irf7 gene renders the host highly susceptible to H1N1 infection. Female, 10-12 weeks old mice were anesthetized by intra-peritoneal injection with Ketamine/Xylazine (85% NaCl (0.9%), 10% Ketamine, 5% Xylazine) with doses adjusted to the individual body weight. Mice were then intra-nasally infected with 20µl virus solution (2x10³ FFU PR8M) or mock-treated with PBS.
2015-07-06 | E-GEOD-66040 | biostudies-arrayexpress
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:Genetic differences are a primary reason for differences in the susceptibility and severity of COVID-19. As induced pluripotent stem (iPS) cells maintain the genetic information of the donor, they can be used to model individual differences in SARS-CoV-2 infection in vitro. We found that human iPS cells expressing the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) (ACE2-iPS cells) can be infected w SARS-CoV-2. In infected ACE2-iPS cells, the expression of SARS-CoV-2 nucleocapsid protein, budding of viral particles, and production of progeny virus, double membrane spherules, and double-membrane vesicles were confirmed. We performed SARS-CoV-2 infection experiments on ACE2-iPS/ embryonic stem (ES) cells from eight individuals. Male iPS/ES cells were more capable of producing the virus compared with female iPS/ES cells. These findings suggest that ACE2-iPS cells can not only reproduce individual differences in SARS-CoV-2 infection in vitro but also are a useful resource to clarify the causes of individual differences in COVID-19 due to genetic differences.
2021-04-18 | GSE166990 | GEO
Project description:The ability to cope with infection by a parasite is one of the major challenges for any host species and is a major driver of evolution. Parasite pressure differs between habitats. It is thought to be higher in tropical regions compared to temporal ones. We infected Drosophila melanogaster from two tropical (Malaysia and Zimbabwe) and two temperate populations (the Netherlands and North Carolina) with the generalist entomopathogenic fungus Beauveria bassiana to examine if adaptation to local parasite pressures led to differences in resistance. Contrary to previous findings we observed increased survival in temperate populations. This, however, is not due to increased resistance to infection per se, but rather the consequence of a higher general vigor of the temperate populations. We also assessed transcriptional response to infection within these flies eight and 24 hours after infection. Only few genes were induced at the earlier time point, most of which are involved in detoxification. In contrast, we identified more than 4,000 genes that changed their expression state after 24 hours. This response was generally conserved over all populations with only few genes being uniquely regulated in the temperate populations. We furthermore found that the American population was transcriptionally highly diverged from all other populations concerning basal levels of gene expression. This was particularly true for stress and immune response genes, which might be the genetic basis for their elevated vigor. mRNA profiles of whole Drosophila melanogaster adult males from an African, American, Asian and European population after infection with Beauveria bassiana. Samples include uninfected controls, 8h after infection and 24h after infection. 3 biological replicates each (2 in the case of American controls).
2015-06-19 | E-GEOD-67177 | biostudies-arrayexpress
Project description:Because activation of the immune response is dependent on extensive changes in gene expression, it is likely that a major component of inter-individual variation in the immune response is ultimately mediated at the level of gene regulation. Here, we examine the influence of genetic variation on inducible gene expression in the murine immune response. We extracted primary CD4 splenocytes from inbred strains A/J, C57BL/6J, BALB/c, DBA/2J, and 129x1/SvJ (3 animals/strain) and measured mRNA transcript levels using microarrays in both basal state and four hours after stimulation with PMA/Ionomycin. We report strain-specific genome-wide differences in mRNA expression between A/J, Balb/c, C57BL/6J, DBA/2J and 129X1/SvJ inbred mice in CD4 splenocytes in basal, stimulated (4hr, PMA/I) states.
2019-09-23 | GSE36551 | GEO
Project description:Bat cells and tissue have elevated basal expression levels of antiviral genes commonly associated with IFNα signalling. Here we show IRF1,3 and 7 levels are elevated in most bat tissues and that basally, IRFs contribute to the expression of type I IFN ligands and high expression of Interferon Regulated Genes (IRGs). CRISPR KO of IRF 1/3/7 in cells reveal distinct subsets of genes affected by each IRF in an IFN-ligand signalling dependent and largely independent manner. As the master regulators of innate immunity, the IRFs, control the kinetics and maintenance of the IRG response and play essential roles in response to IAV, HSV1, PRV3M and MERS-CoV infection. With its differential expression compared to human, this highlights a critical role for basal IRF expression in viral responses and potentially immune cell development in bats with relevance for IRF function in human biology.
2020-10-23 | PXD021982 | JPOST Repository
Project description:Ribosomes are highly abundant cellular machines that perform the essential task of translating the genetic code into proteins. Cellular translation activity is finely tuned and proteostasis insults, such as those incurred upon viral infection, activate stress signaling pathways that result in translation reprogramming. Viral infection selectively shuts down host mRNA while redistributing ribosomes for selective translation of viral mRNAs. The intricacies of this selective ribosome shuffle from host to viral mRNAs are poorly understood. Here, we uncover a role for the ribosome associated quality control (RQC) factor ZNF598, a sensor for collided ribosomes, as a critical factor for vaccinia virus mRNA translation. Collided ribosomes are sensed by ZNF598, which ubiquitylates 40S subunit proteins uS10 and eS10 and thereby initiates RQC-dependent nascent chain degradation and ribosome recycling. We show that vaccinia infection in human cells enhances uS10 ubiquitylation indicating an increased burden on RQC pathways during viral propagation. Consistent with an increased RQC demand, we demonstrate that vaccinia virus replication is impaired in cells which either lack ZNF598 or contain a ubiquitylation deficient version of uS10. Using SILAC-based proteomics and concurrent RNAseq analysis, we determine that host translation of vaccinia virus mRNAs is compromised in cells that lack RQC activity as compared to control cells whereas there was little evidence of differences in host or viral transcription. Additionally, vaccinia virus infection resulted in a loss of cellular RQC activity, suggesting that ribosomes engaged in viral protein production recruit ZNF598 away from its function in host translation. Thus, co-option of ZNF598 by vaccinia virus plays a critical role in translational reprogramming that is needed for optimal viral propagation.
2021-01-05 | MSV000086660 | MassIVE
Project description:The airway epithelium is a key protective barrier whose integrity is preserved by the self-renewal and differentiation of basal progenitor cells. Epithelial cells are central to the pathogenesis of multiple chronic lung diseases for which age is a principle risk factor. Children are also less susceptible to SARS-CoV-2 infection, suffer less severe symptoms than adults and have a lower rate of mortality. Few studies have addressed differences between airway epithelial cells in children and adults. Here, we perform bulk RNA sequencing studies in laser-captured whole epithelium, FACS-sorted basal cells and cultured basal cells, as well as in vitro cell proliferation experiments, to address the intrinsic molecular differences between paediatric and adult airway basal cells. We find that, while the cellular composition of the paediatric and adult tracheal epithelium is broadly similar, in cell culture, paediatric airway epithelial cells displayed higher colony forming ability, better in vitro growth and outcompeted adult cells in competitive proliferation assays. Although recurring differences between airway epithelial gene expression were seen between samples from children and adults, RNA sequencing showed broad conservation of transcriptional programmes. Genes associated with SARS-CoV-2 infection were not differentially expressed between children and adults, although individuals showed some variability in their expression of viral infection-associated genes. Our results chart important cell intrinsic differences in transcriptional profile and regenerative capacity between tracheal epithelial cells of children and adults.
2020-04-20 | GSE148817 | GEO