Genome-wide CRISPR/Cas9 library screening identifies genes regulating the IFN signalling pathways.
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE143467 | GEO | 2020/01/11
REPOSITORIES: GEO
Similar Datasets
Project description:A. Esteban Hernandez-Vargas & Michael Meyer-Hermann. Innate Immune System Dynamics to Influenza Virus. IFAC Proceedings Volumes 45, 18 (2012).
The understanding of how influenza virus infection activates the immune system is crucial to designing prophylactic and therapeutic strategies against the infection. Nevertheless, the immune response to influenza virus infection is complex and remains largely unknown. In this paper we focus in the innate immune response to influenza virus using a mathematical model, based on interferon-induced resistance to infection of respiratory epithelial cells and the clearance of infected cells by natural killers. Simulation results show the importance of IFN-I to prevent new infections in epithelial cells and to stop the viral explosion during the first two days after infection. Nevertheless, natural killers response might be the most relevant for the first depletion in viral load due to the elimination of infected cells. Based on the reproductive number, the innate immune response is important to control the infection, although it would not be enough to clear completely the virus. The effective coordination between innate and adaptive immune response is essential for the virus eradication.
2024-09-02 | BIOMD0000000710 | BioModels
Project description:Massive mortalities have been observed in France since 2008 on spat and juvenile Pacific oysters, Crassostrea gigas. A herpes virus called OsHV-1, easily detectable by PCR, has been implicated in the mortalities as demonstrated by the results of numerous field studies linking mortality with OsHV-1 prevalence. Moreover, experimental infections using viral particles have documented the pathogenicity of OsHV-1. The physiological responses of host to pathogen are not well known. In this study, a number of genes involved in the response to viral challenge have been identified and can be considered as confirmation of the role of the virus in the observed mortality. The aim of this study was to understand mechanisms brought into play against the virus during infection in the field. A microarray assay has been developed for a major part of the oyster genome and used for studying the host transcriptome. Spat with and without detectable OsHV-1 infection were compared by microarray during mortality episodes. The result allowed establishment of a hypothetic scheme of the host cell’s infection by, and response to, the pathogen. This response seems to be different to “sensu stricto” innate immunity through genic regulation of the virus life cycle. . Some regulatory response against the virus may explain that some oysters are able to survive infection by regulation of the viral genes associated with the OsHV-1 life cycle.
2013-06-28 | GSE46249 | GEO
Project description:Massive mortalities have been observed in France since 2008 on spat and juvenile Pacific oysters, Crassostrea gigas. A herpes virus called OsHV-1, easily detectable by PCR, has been implicated in the mortalities as demonstrated by the results of numerous field studies linking mortality with OsHV-1 prevalence. Moreover, experimental infections using viral particles have documented the pathogenicity of OsHV-1. The physiological responses of host to pathogen are not well known. In this study, a number of genes involved in the response to viral challenge have been identified and can be considered as confirmation of the role of the virus in the observed mortality. The aim of this study was to understand mechanisms brought into play against the virus during infection in the field. A microarray assay has been developed for a major part of the oyster genome and used for studying the host transcriptome. Spat with and without detectable OsHV-1 infection were compared by microarray during mortality episodes. The result allowed establishment of a hypothetic scheme of the host cell’s infection by, and response to, the pathogen. This response seems to be different to “sensu stricto” innate immunity through genic regulation of the virus life cycle. . Some regulatory response against the virus may explain that some oysters are able to survive infection by regulation of the viral genes associated with the OsHV-1 life cycle. Gene expression was measured from four individual animals of three sites, an oyster production area where mortalities on spat was observed in Spring (BL: Blainville sur mer) and two sanctuary sites (CRIC, Cricqueville en Bessin without production and CAB, an offshore storage structure)
2013-06-28 | E-GEOD-46249 | biostudies-arrayexpress
Project description:Baris Hancioglu, David Swigon & Gilles Clermont. A dynamical model of human immune response to influenza A virus infection. Journal of Theoretical Biology 246, 1 (2007).
We present a simplified dynamical model of immune response to uncomplicated influenza A virus (IAV) infection, which focuses on the control of the infection by the innate and adaptive immunity. Innate immunity is represented by interferon-induced resistance to infection of respiratory epithelial cells and by removal of infected cells by effector cells (cytotoxic T-cells and natural killer cells). Adaptive immunity is represented by virus-specific antibodies. Similar in spirit to the recent model of Bocharov and Romanyukha [1994. Mathematical model of antiviral immune response. III. Influenza A virus infection. J. Theor. Biol. 167, 323-360], the model is constructed as a system of 10 ordinary differential equations with 27 parameters characterizing the rates of various processes contributing to the course of disease. The parameters are derived from published experimental data or estimated so as to reproduce available data about the time course of IAV infection in a naïve host. We explore the effect of initial viral load on the severity and duration of the disease, construct a phase diagram that sheds insight into the dynamics of the disease, and perform sensitivity analysis on the model parameters to explore which ones influence the most the onset, duration and severity of infection. To account for the variability and speed of adaptation of the adaptive response to a particular virus strain, we introduce a variable that quantifies the antigenic compatibility between the virus and the antibodies currently produced by the organism. We find that for small initial viral load the disease progresses through an asymptomatic course, for intermediate value it takes a typical course with constant duration and severity of infection but variable onset, and for large initial viral load the disease becomes severe. This behavior is robust to a wide range of parameter values. The absence of antibody response leads to recurrence of disease and appearance of a chronic state with nontrivial constant viral load.
2024-09-02 | BIOMD0000000711 | BioModels
Project description:Natural SIV infection of sooty mangabeys (SMs) does not progress to disease despite chronic virus replication. In contrast to pathogenic SIV infection of rhesus macaques (RMs), chronic SIV infection of SMs is characterized by low immune activation. To elucidate the mechanisms underlying this phenotype, we longitudinally assessed host gene expression in SIV-infected SMs and RMs. We found that acute SIV infection of SMs is consistently associated with a robust innate immune response, including widespread up-regulation of interferon-stimulated genes (ISGs). Our findings indicate that active immune regulatory mechanisms, rather than intrinsically attenuated innate immune responses, underlie the low immuneactivation of chronically SIV-infected SMs.
2010-03-08 | GSE16147 | GEO
Project description:Natural SIV infection of sooty mangabeys (SMs) does not progress to disease despite chronic virus replication. In contrast to pathogenic SIV infection of rhesus macaques (RMs), chronic SIV infection of SMs is characterized by low immune activation. To elucidate the mechanisms underlying this phenotype, we longitudinally assessed host gene expression in SIV-infected SMs and RMs. We found that acute SIV infection of SMs is consistently associated with a robust innate immune response, including widespread up-regulation of interferon-stimulated genes (ISGs). Our findings indicate that active immune regulatory mechanisms, rather than intrinsically attenuated innate immune responses, underlie the low immuneactivation of chronically SIV-infected SMs. We infected 5 SMs with SIVsmm and assessed their gene expression in RNA derived from whole blood at 3,7,10,14,30 and 180 days post-infection using Rhesus Affymetrix GeneChips. As a comparison, we also analyzed gene expression in 4 RMs infected with SIVsmm, and 8 RMs infected with SIVmac239, a classical pathogenic SIV.
2010-03-08 | E-GEOD-16147 | biostudies-arrayexpress
Project description:The immune system continually battles against pathogen-induced pressures, which often leads to the evolutionary expansion of immune gene families in a species-specific manner. For example, the pals gene family expanded to 39 members in the Caenorhabditis elegans genome, in comparison to a single mammalian pals ortholog. Our previous studies have revealed that two members of this family, pals-22 and pals-25, act as antagonistic paralogs to control the Intracellular Pathogen Response (IPR). The IPR is a protective transcriptional response, which is activated upon infection by two molecularly distinct natural intracellular pathogens of C. elegans – the Orsay virus and the fungus Nematocida parisii from the microsporidia phylum. In this study, we identify a previously uncharacterized member of the pals family, pals-17, as a newly described negative regulator of the IPR. pals-17 mutants show constitutive upregulation of IPR gene expression, increased immunity against intracellular pathogens, as well as impaired development and reproduction. We also find that two other previously uncharacterized pals genes, pals-20 and pals-16, are positive regulators of the IPR, acting downstream of pals-17. These positive regulators reverse the effects caused by the loss of pals-17 on IPR gene expression, immunity and development. We show that the negative IPR regulator protein PALS-17 and the positive IPR regulator protein PALS-20 colocalize inside intestinal epithelial cells, which are the sites of infection for IPR-inducing pathogens. In summary, our study demonstrates that several pals genes from the expanded pals gene family act as ON/OFF switch modules to regulate a balance between organismal development and immunity against natural intracellular pathogens in C. elegans.
2023-04-28 | GSE229142 | GEO
Project description:The immune system continually battles against pathogen-induced pressures, which often leads to the evolutionary expansion of immune gene families in a species-specific manner. For example, the pals gene family expanded to 39 members in the Caenorhabditis elegans genome, in comparison to a single mammalian pals ortholog. Our previous studies have revealed that two members of this family, pals-22 and pals-25, act as antagonistic paralogs to control the Intracellular Pathogen Response (IPR). The IPR is a protective transcriptional response, which is activated upon infection by two molecularly distinct natural intracellular pathogens of C. elegans – the Orsay virus and the fungus Nematocida parisii from the microsporidia phylum. In this study, we identify a previously uncharacterized member of the pals family, pals-17, as a newly described negative regulator of the IPR. pals-17 mutants show constitutive upregulation of IPR gene expression, increased immunity against intracellular pathogens, as well as impaired development and reproduction. We also find that two other previously uncharacterized pals genes, pals-20 and pals-16, are positive regulators of the IPR, acting downstream of pals-17. These positive regulators reverse the effects caused by the loss of pals-17 on IPR gene expression, immunity and development. We show that the negative IPR regulator protein PALS-17 and the positive IPR regulator protein PALS-20 colocalize inside intestinal epithelial cells, which are the sites of infection for IPR-inducing pathogens. In summary, our study demonstrates that several pals genes from the expanded pals gene family act as ON/OFF switch modules to regulate a balance between organismal development and immunity against natural intracellular pathogens in C. elegans.
2023-04-28 | GSE229164 | GEO
Project description:Rift Valley fever virus causes severe disease in humans and livestock and in some cases can be fatal. There is concern about the use of Rift Valley fever virus as a bioweapon since it can be transmitted through the air, and there are no vaccines or antiviral treatments. Airborne transmission of the virus causes severe inflammation of the brain, yet little is known about the immune response against the virus in this organ. Here, we investigated the immune response in the brain to Rift Valley fever virus following intranasal infection. We determined that microglia, the resident immune cells of the brain, initiate a robust response to Rift Valley fever virus infection and identified a key immune pathway that is critical for the ability of microglia to respond to infection. When this immune pathway is rendered non-functional, mice have a dysregulated response to infection in the brain.
2022-04-27 | GSE200881 | GEO
Project description:Human transmission of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the causative pathogen of the coronavirus disease 2019 (COVID-19) pandemic, is exerting a massive health and socioeconomic burden. The virus infects pneumocytes, also known as alveolar epithelial type 2 (AT2) cells, leading to impaired gas exchange and acute lung injury, but the mechanisms driving infection and pathology are unclear. Here, we report a quantitative phosphoproteomic time-course survey of a validated human AT2 cell model, derived from induced pluripotent stem cells (iPSCs), that reveals rapid, profound and switch-like rewiring of lung cell functional modules upon SARS-CoV-2 infection. Maladaptive responses driven by viral propagation include altered host cell signaling pathways, remodeled host translational processes, impaired RNA processing, cytoskeletal-microtubule disruption coincident with interphase arrest, and a pronounced innate immune response. Our study provides a data-rich resource that defines the native host systems hijacked by SARS-CoV-2 and potential therapeutic avenues for COVID-19.
2020-11-20 | PXD020183 | Pride