Dual RNA-Seq characterization of host and pathogen gene expression in liver cells infected with Crimean-Congo Hemorrhagic Fever Virus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA549926 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9332030_1.fastq.gz | Fastqsanger.gz | |||
| SRR9332030_2.fastq.gz | Fastqsanger.gz | |||
| SRR9332040_1.fastq.gz | Fastqsanger.gz | |||
| SRR9332040_2.fastq.gz | Fastqsanger.gz | |||
| SRR9332031_1.fastq.gz | Fastqsanger.gz |
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Project description:A NanoString targeted gene panel was used to elucidate the transcriptomic changes occurring in non-human primate whole blood during Crimean Congo Hemorrhagic Fever Virus infection.
2021-09-23 | GSE169698 | GEO
Project description:Crimean-Congo hemorrhagic fever (CCHF), caused by Crimean-Congo hemorrhagic fever virus (CCHFV), is on the World Health Organizations list over emerging pathogens and prioritized diseases. With global distribution, high fatality rate and no approved treatment or vaccine, CCHF constitute a treat against the global health. In the current study we show full protection of mice against lethal CCHFV infection due to mRNA-LNP vaccination. IFNAR-/- mice received two immunizations with either mRNA-LNP encoding for the CCHFV nucleoprotein, glycoproteins or a combination of both. While unvaccinated mice showed clear signs of severe disease, vaccinated mice was significantly protected. Vaccine induced immune responses due to vaccination was evaluated both in IFNAR-/- and immunocompetent mice and a strong humoral and cellular immune response was observed in both mouse models with high titers of neutralizing antibodies and primed T-cells. In addition, we conducted a proteomic analysis on liver samples from vaccinated and unvaccinated mice after CCHFV infection to determine the effect of vaccination on the protein profile. Similar to what has been observed in humans due to vaccination, there was an effect on metabolic pathways. In conclusion, this study shows very promising results regarding development of a vaccine against CCHFV.
2021-11-15 | PXD023300 | Pride
Project description:Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus that can cause a hemorrhagic fever in humans, with a case fatality rate of up to 50%. Cases of CCHFV have been reported in Africa, Asia, and southern Europe; and recently, due to the expanding range of its vector, autochthonous cases have been reported in Spain. Although it was discovered over 70 years ago, our understanding of the pathogenesis of this virus remains limited. We used RNA-Seq in two human liver cell lines (HepG2 and Huh7) infected with CCHFV (strain Ib 10200), to examine kinetic changes in host expression and viral replication simultaneously at 24 and 72 hours post infection. Through this, numerous host pathways were identified that were modulated by the virus including: antiviral response and endothelial cell leakage. Notably, DDX60, a cytosolic component of the RIG-I signalling pathway and OAS2 were both shown to be dysregulated. Interestingly, the PTPRR gene was induced in Huh7 cells. This has been associated with the TLR9 signalling cascade, and polymorphisms in the TLR9 gene have been associated with poor outcomes in patients. Additionally, we whole-genome sequenced CCHFV to assess viral diversity over time, and its relationship to the host response. As a result, we have demonstrated that through next-generation mRNA deep-sequencing it is possible to not only examine mRNA gene expression, but also to examine viral evolution. This demonstrates a proof-of-principle that specimens can be analyzed to identify both the virus, and host biomarkers that may have implications for prognosis.
2020-03-26 | GSE133086 | GEO
Project description:The pathogenesis and host viral interactions of the Crimean–Congo hemorrhagic fever virus (CCHFV) are convoluted and have not been evaluated previously. To understand the host immune responses against CCHFV, we have performed a global transcriptomic analysis of peripheral blood mononuclear cells from a longitudinal cohort of CCHF patients who survived, and a temporal untargeted proteomics analysis of CCHFV infected cells. Our results indicate that during the acute phase of CCHFV infection, metabolic reprogramming of the host towards central carbon metabolism including glycolysis/gluconeogenesis occurs. This could potentially be regulated by the PI3K/Akt, HIF-1, FoxO, and AMPK signaling pathways and play a central role in viral replication. Moreover, key interferon stimulating genes (ISGs: ISG12, ISG15, ISG20 and MXs: Mx1 and Mx2) are activated during infection, suggesting a role for type I and II interferon-mediated antiviral mechanisms. Targeting type I interferon response through metabolic rewiring could be an attractive therapeutic intervention for CCHFV.
2022-05-04 | PXD022672 | Pride
Project description:Crimean-Congo hemorrhagic fever (CCHF) caused by CCHF virus (CCHFV) is one of the epidemic-prone diseases prioritized by the World Health Organisation as public health emergency with an urgent need for accelerated research. The trajectory of host response against CCHFV is multifarious and remains unknown. Here, we reported the temporal spectrum of pathogenesis following the CCHFV infection using genome-wide blood transcriptomics analysis followed by advanced systems biology analysis, temporal immune-pathogenic alterations, and context-specific progressive and postinfection genome-scale metabolic models (GSMM) on samples collected during the acute (T0), early convalescent (T1), and convalescent-phase (T2). The interplay between the retinoic acid-inducible gene-I-like/nucleotide-binding oligomerization domain-like receptor and tumor necrosis factor signaling governed the trajectory of antiviral immune responses. The rearrangement of intracellular metabolic fluxes toward the amino acid metabolism and metabolic shift toward oxidative phosphorylation and fatty acid oxidation during acute CCHFV infection determine the pathogenicity. The upregulation of the tricarboxylic acid cycle during CCHFV infection, compared to the noninfected healthy control and between the severity groups, indicated an increased energy demand and cellular stress. The upregulation of glycolysis and pyruvate metabolism potentiated energy generation through alternative pathways associated with the severity of the infection. The downregulation of metabolic processes at the convalescent phase identified by blood cell transcriptomics and single-cell type proteomics of five immune cells (CD4+ and CD8+ T cells, CD14+ monocytes, B cells, and NK cells) potentially leads to metabolic rewiring through the recovery due to hyperactivity during the acute phase leading to post-viral fatigue syndrome.
2023-10-11 | PXD038929 | Pride
Project description:Host response transcriptomic analysis of Crimean-Congo hemorrhagic fever pathogenesis in the cynomolgus macaque model
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Project description:Crimean-Congo Hemorrhagic Fever Virus raw sequence reads
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Project description:Zaire ebolavirus (ZEBOV) is among the deadliest known human pathogens, causing severe hemorrhagic fever with high case fatality rates ranging from 70-90%. The lack of effective vaccines or treatment available for ZEBOV renders this pathogen as a significant global biodefense threat, as evidenced by the current, highly lethal outbreak of a novel ZEBOV variant in western Africa. Existing mouse models of lethal ZEBOV infection do not reproduce hallmark symptoms of Ebola hemorrhagic fever (EHF) including prolonged blood coagulation, acute hepatitis, disseminated intravascular coagulation (DIC), and death from hemorrhagic shock, thus restricting pathogenesis studies to non-human primates (NHP). This has prevented rapid evaluation of countermeasures in outbreak scenarios, and impeded a comprehensive understanding of how host responses to infection contribute to severe EHF disease. Here we demonstrate that mice from the Collaborative Cross (CC), a panel of reproducible, recombinant inbred animals that span the genetic breadth of three murine subspecies, are susceptible to a spectrum of disease phenotypes following ZEBOV infection. In contrast to C57Bl6/J mice, which develop lethal disease without symptoms of EHF, CC recombinant inbred intercrossed (CC-RIX) lines develop either complete resistance to lethal disease or severe EHF characterized by prolonged coagulation times and 100% mortality. Disease resistance and survival is not dependent on viral tropism, as both resistant and EHF-susceptible lines show similar inflammation and cytopathic effect in target organs. Transcriptomics reveal potential mechanisms for both induction of severe hemorrhage in EHF mediated by IL-6 and vascular activation, and resistance to lethal infection by induction of lymphocyte differentiation and cellular adhesion. These data demonstrate that host responses specific to unique genetic backgrounds determine susceptibility to hemorrhagic syndrome independent of virus replication. The CC represents a novel mouse model for studying EHF pathogenesis, and we anticipate that it will be applied immediately to developing and evaluating therapeutic countermeasures. Microarrays were performed on liver and spleen samples from mice collected at days 1, 3, and 5 post-infection with mouse adapted Zaire ebolavirus or from time-matched mock-infected animals.
2014-05-01 | E-GEOD-57214 | biostudies-arrayexpress
Project description:Zaire ebolavirus (ZEBOV) is among the deadliest known human pathogens, causing severe hemorrhagic fever with high case fatality rates ranging from 70-90%. The lack of effective vaccines or treatment available for ZEBOV renders this pathogen as a significant global biodefense threat, as evidenced by the current, highly lethal outbreak of a novel ZEBOV variant in western Africa. Existing mouse models of lethal ZEBOV infection do not reproduce hallmark symptoms of Ebola hemorrhagic fever (EHF) including prolonged blood coagulation, acute hepatitis, disseminated intravascular coagulation (DIC), and death from hemorrhagic shock, thus restricting pathogenesis studies to non-human primates (NHP). This has prevented rapid evaluation of countermeasures in outbreak scenarios, and impeded a comprehensive understanding of how host responses to infection contribute to severe EHF disease. Here we demonstrate that mice from the Collaborative Cross (CC), a panel of reproducible, recombinant inbred animals that span the genetic breadth of three murine subspecies, are susceptible to a spectrum of disease phenotypes following ZEBOV infection. In contrast to C57Bl6/J mice, which develop lethal disease without symptoms of EHF, CC recombinant inbred intercrossed (CC-RIX) lines develop either complete resistance to lethal disease or severe EHF characterized by prolonged coagulation times and 100% mortality. Disease resistance and survival is not dependent on viral tropism, as both resistant and EHF-susceptible lines show similar inflammation and cytopathic effect in target organs. Transcriptomics reveal potential mechanisms for both induction of severe hemorrhage in EHF mediated by IL-6 and vascular activation, and resistance to lethal infection by induction of lymphocyte differentiation and cellular adhesion. These data demonstrate that host responses specific to unique genetic backgrounds determine susceptibility to hemorrhagic syndrome independent of virus replication. The CC represents a novel mouse model for studying EHF pathogenesis, and we anticipate that it will be applied immediately to developing and evaluating therapeutic countermeasures.
2014-05-01 | GSE57214 | GEO
Project description:Rhesus macaques (Macaca mulatta) infected with a lethal dose of lymphocytic choriomeningitis virus-strain WE (LCMV-WE) provide a model for Lassa fever virus infection of man. Like Lassa fever in human beings, disease begins with flu-like symptoms but can progress to morbidity fairly rapidly. Previously, we profiled the blood transcriptome of LCMV-infected monkeys (M. Djavani et al. J. Virol. 2007: PMID 17522210) showing distinct pre-viremic and viremic stages that discriminated between virulent and benign infections. In the present study, changes in liver gene expression from macaques infected with virulent LCMV-WE were compared to gene expression in uninfected monkeys as well as to monkeys that were infected but not diseased. We observed gene expression changes that occurred before the viremic stage of the disease, and could potentially serve as biomarkers that discriminate between exposure to a hemorrhagic fever virus and exposure to a benign virus. Based on a functional pathway analysis of differentially expressed genes, virulent LCMV-WE had a much broader effect on liver cell function than non-virulent virus. During the first few days of infection, virulent virus impacted gene expression associated with the generation of energy, such as fatty acid metabolism and glucose metabolism, with the complement and coagulation cascades, and with steroid metabolism, MAPK signaling and cell adhesion. For example, the energy profile resembled that of an organism entering starvation: acetyl-CoA carboxylase, a key enzyme of fatty acid synthesis, was shut down and gene products involved in gluconeogenesis were up-regulated. In conclusion, this study identifies several potential gene markers of LCMV-WE-associated liver disease and contributes to the database of gene expression changes correlated with LCMV pathogenesis in primates. 6 groups: uninfected controls, LCMV-WE infected (pre-viremic; day 1 to day 3), LCMV-WE infected (viremic; day 4 to day 7), LCMV-WE infected (post-viremic; day 8 to day 12), LCMV-Armstrong (LCMV-ARM; non-virulent strain) infected, and LCMV-ARM/LCMV-WE infected but not diseased. Each sample is from the liver of a different rhesus macaque.
2010-06-16 | E-GEOD-12254 | biostudies-arrayexpress