Bat metagenome
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA656060 | ENA |
REPOSITORIES: ENA
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Project description:Bats are the most important natural reservoirs for a variety of emerging viruses that cause several illnesses in humans and other mammals. Increased viral shedding by bats is thought to be linked to an increased ability of many bat species to tolerate viral infection. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19, is thought to have originated in bats, since viruses with high sequence similarity have been detected in bat feces. However, there is no robust in vitro model for assessing the SARS-CoV-2 infection in the bat GI tract. Here, we established gastrointestinal organoid cultures from Jamaican fruit bats (JFB, Artibeus jamaicensis), which replicated the characteristic morphology of the gastrointestinal epithelium and showed tissue specific gene expression patterns and cell differentiation. To analyze whether JFB intestinal epithelial cells are susceptible to SARS-CoV-2, we performed in vitro infection experiments. Increased SARS-CoV-2 RNA was found in both cell lysates and supernatants from the infected organoids after 48 h, and sgRNA also was detected, indicating that the JFB intestinal epithelium supports limited viral replication. However, no infectious virus was released into the culture media, and no cytopathic effects were observed. Gene expression studies revealed a significant induction of type I interferon and inflammatory cytokine genes in response to active SARS-CoV-2 virus but not to TLR agonist treatment. Untargeted analysis of the organoid proteome using data-independent acquisition mass spectrometry (DIA-MS) revealed a significant increase in proteins and pathways associated with inflammatory signaling, cell turnover and repair, and SARS-CoV-2 infection. Collectively, our data suggest that primary intestinal epithelial cells from JFBs are largely resistant to SARS-CoV-2 infection and cell damage, likely because they are able to mount a strong antiviral interferon and regenerative response upon infection.
2024-01-26 | PXD036016 | Pride
Project description:Differential expression was determined in Calu-3 cells between mock infected and infection with either Human coronavirus EMC and SARS coronavirus at different times post infection. Calu-3 2B4 cells were infected with Human Coronavirus EMC 2012 (HCoV-EMC) or mock infected. Samples were collected 0, 3, 7, 12, 18 and 24 hpi. There are 3 mock and 3 infected replicates for each time point, except for 12 hpi for which there are only 2 infected replicates (one replicate did not pass RNA quality check). There were no mock sampes at 18 hpi, and therefore infected samples at 18 hpi were compared with mocks at 24 hpi. For direct comparison with SARS-CoV infected cells, raw data from HCoV-EMC experiments were quantile normalized together with the SARS-CoV dataset (GEO Series accession number GSE33267).
2013-05-03 | E-GEOD-45042 | biostudies-arrayexpress
Project description:Despite the wide availability of several safe and effective vaccines that can prevent severe COVID-19 disease, the emergence of SARS-CoV-2 variants of concern (VOC) that can partially evade vaccine immunity remains a global health concern. In addition, the emergence of highly mutated and neutralization-resistant SARS-CoV-2 VOCs such as BA.1 and BA.5 that can partially or fully evade (1) many therapeutic monoclonal antibodies in clinical use underlines the need for additional effective treatment strategies. Here, we characterize the antiviral activity of GS-5245, Obeldesivir (ODV), an oral prodrug of the parent nucleoside GS-441524, which targets the highly conserved RNA-dependent viral RNA polymerase (RdRp). Importantly, we show that GS-5245 is broadly potent in vitro against alphacoronavirus HCoV-NL63, severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-related Bat-CoV RsSHC014, Middle East Respiratory Syndrome coronavirus (MERS-CoV), SARS-CoV-2 WA/1, and the highly transmissible SARS-CoV-2 BA.1 Omicron variant in vitro and highly effective as antiviral therapy in mouse models of SARS-CoV, SARS-CoV-2 (WA/1), MERS-CoV and Bat-CoV RsSHC014 pathogenesis. In all these models of divergent coronaviruses, we observed protection and/or significant reduction of disease metrics such as weight loss, lung viral replication, acute lung injury, and degradation in pulmonary function in GS-5245-treated mice compared to vehicle controls. Finally, we demonstrate that GS-5245 in combination with the main protease (Mpro) inhibitor nirmatrelvir had increased efficacy in vivo against SARS-CoV-2 compared to each single agent. We also evalulate the effect of antiviral therapy on host gene expression using RNAseq and show that therapeutic intervention reduces host inflammatory response as compared to vehicle controls during acute SARS-CoV-2 infection. Altogether, our data supports the continuing clinical evaluation of GS-5245 in humans infected with COVID-19, including as part of a combination antiviral therapy, especially in populations with the most urgent need for more efficacious and durable interventions.
2024-04-15 | GSE254256 | GEO
Project description:To evaluate the gene expression profiling of peripheral leukocytes in different outcomes of SARS-CoV-2 infections, whole blood samples were collected from individuals with positive SARS-CoV-2 nasopharyngeal swab by RT-PCR (54 patients) and healthy uninfected individuals (12 volunteers). Infected patients were classified into mild, moderate, severe and critical groups according to a modified statement in the Novel Coronavirus Pneumonia Diagnosis and Treatment Guideline. Blood were collected into EDTA tubes and the buffy coat samples were stored in TRIzol reagent at -80 °C until use for RNA extraction. Affymetrix Clariom S array was used to perform the high-throughput gene expression profiling. Microarray analyses were performed using APT Affymetrix software, R packages and Bioconductor libraries. This systemic view of SARS-CoV-2 infections through blood transcriptomics will foster the understanding about molecular mechanisms and immunopathological processes involved in COVID-19 disease and its different outcomes.
2022-04-29 | E-MTAB-11240 | biostudies-arrayexpress
Project description:We performed genome-wide CRISPR KO screens in human Huh7.5.1 cells to select for mutations that render host cells resistant to viral infection by SARS-CoV-2, human coronavirus 229E and OC43.
2020-10-16 | E-MTAB-9638 | biostudies-arrayexpress
Project description:Abstract: The COVID-19 (Coronavirus disease-2019) pandemic, caused by the SARS-CoV-2 coronavirus, has highlighted emergent viruses as significant threats to public health and the global economy. SARS-CoV-2 is closely related to the more lethal but less transmissible coronaviruses SARS-CoV-1 and MERS-CoV. Here, we have carried out comparative viral-human protein-protein interaction and viral protein localization analysis for all three viruses. We find that proteins often do not change localization across viruses but their sequence divergence dictates differences in host interactions. Functional genetic screening identified host factors that functionally impinge on coronavirus proliferation, including Tom70, a mitochondrial chaperone protein that interacts with both SARS-CoV-1 and SARS-CoV-2 Orf9b, an interaction we structurally characterized using cryoEM. Combining genetically validated host factors with both COVID-19 patient genetic data and medical billing records identified important molecular mechanisms (IL-17 regulation) and drug treatments (sigma-1 receptor ligands) that merit further molecular and clinical study.
2020-10-16 | PXD021588 | Pride
Project description:All coronaviruses known to have recently emerged as human pathogens probably originated in bats1. Here we use a single experimental platform based on immunodeficient mice implanted with human lung tissue (hereafter, human lung-only mice (LoM)) to demonstrate the efficient in vivo replication of severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as well as two endogenous SARS-like bat coronaviruses that show potential for emergence as human pathogens. Virus replication in this model occurs in bona fide human lung tissue and does not require any type of adaptation of the virus or the host. Our results indicate that bats contain endogenous coronaviruses that are capable of direct transmission to humans. Our detailed analysis of in vivo infection with SARS-CoV-2 in human lung tissue from LoM showed a predominant infection of human lung epithelial cells, including type-2 pneumocytes that are present in alveoli and ciliated airway cells. Acute infection with SARS-CoV-2 was highly cytopathic and induced a robust and sustained type-I interferon and inflammatory cytokine and chemokine response. Finally, we evaluated a therapeutic and pre-exposure prophylaxis strategy for SARS-CoV-2 infection. Our results show that therapeutic and prophylactic administration of EIDD-2801?an oral broad-spectrum antiviral agent that is currently in phase II/III clinical trials?markedly inhibited SARS-CoV-2 replication in vivo, and thus has considerable potential for the prevention and treatment of COVID-19.
2020-09-23 | GSE155286 | GEO
Project description:Discovery and characterization of a novel bat coronavirus sheds light on the origin of emerging infectious diseases
| PRJNA756962 | ENA
Project description:Background: The recent emergence of a novel coronavirus in the Middle East (designated MERS-CoV) is a reminder of the zoonotic potential of coronaviruses and the severe disease these etiologic agents can cause in humans. Clinical features of Middle East respiratory syndrome (MERS) include severe acute pneumonia and renal failure that is highly reminiscent of severe acute respiratory syndrome (SARS) caused by SARS-CoV. The host response is a key component of highly pathogenic respiratory virus infection. Here, we computationally analyzed gene expression changes in a human airway epithelial cell line infected with two genetically distinct MERS-CoV strains obtained from human patients, MERS-CoV-EMC (designated EMC) and MERS-CoV-London (designated LoCoV). Results: Using topological techniques, such as persistence homology and filtered clustering, we characterized the host response system to the different MERS-CoVs, with LoCoV inducing early kinetic changes, between 3 and 12 hours post infection, compared to EMC. Robust transcriptional changes distinguished the two MERS-CoV strains predominantly at the late time points. Combining statistical analysis of infection and cytokine-stimulated treatment transcriptomics, we identified differential innate and pro-inflammatory responses between the two virus strains, including up-regulation of extracellular remodeling genes following LoCoV infection and differential pro-inflammatory responses between the two strains. Conclusions: These transcriptional differences may be the result of amino acid differences in viral proteins known to modulate innate immunity against MERS infection. Triplicate wells of Calu-3 2B4 cells were infected with Human Coronavirus EMC 2012 (HCoV-EMC) or time-matched mock infected. Cells were harvested at 0, 3, 7, 12, 18 and 24 hours post-infection (hpi), RNA extracted and transcriptomics analyzed by microarray.
2014-08-31 | E-GEOD-56677 | biostudies-arrayexpress
Project description:Bat coronavirus Genome sequencing and assembly
| PRJNA380522 | ENA