Comparative Transcriptomics in Ebola-Makona infected Ferrets, Non-human Primates, and Humans
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ABSTRACT:
PROVIDER: PRJNA475581 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7290900_1.fastq.gz | Fastqsanger.gz | |||
| SRR7290900_2.fastq.gz | Fastqsanger.gz | |||
| SRR7290910_1.fastq.gz | Fastqsanger.gz | |||
| SRR7290910_2.fastq.gz | Fastqsanger.gz | |||
| SRR7290911_1.fastq.gz | Fastqsanger.gz |
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Project description:The domestic ferret has recently been described as a uniformly lethal model of infection for three species of Ebolavirus known to be pathogenic to humans. Reagents to systematically analyze the ferret host response to infection are lacking; however, the recent publication of a draft ferret genome has opened the potential for transcriptional analysis of ferret models of disease. In this work, we present comparative analysis of longitudinally sampled blood taken from ferrets and non-human primates infected with lethal doses of the Makona strain of Zaire ebolavirus. Strong induction of proinflammatory and prothrombotic signaling programs were present in both ferrets and non-human primates and both transcriptomes were similar to previously published datasets of fatal cases of human Ebola virus infection.
2018-08-26 | GSE115620 | GEO
Project description:The domestic ferret has recently been described as a uniformly lethal model of infection for three species of Ebolavirus known to be pathogenic to humans. Reagents to systematically analyze the ferret host response to infection are lacking; however, the recent publication of a draft ferret genome has opened the potential for transcriptional analysis of ferret models of disease. In this work, we present comparative analysis of longitudinally sampled blood taken from ferrets and non-human primates infected with lethal doses of the Makona strain of Zaire ebolavirus. Strong induction of proinflammatory and prothrombotic signaling programs were present in both ferrets and non-human primates and both transcriptomes were similar to previously published datasets of fatal cases of human Ebola virus infection.
2018-08-26 | GSE115785 | GEO
Project description:The domestic ferret is a uniformly lethal model of infection for 3 species of Ebolavirus known to be pathogenic in humans. Reagents to systematically analyze the ferret host response to infection are lacking; however, the recent publication of a draft ferret genome has opened the potential for transcriptional analysis of ferret models of disease. In this work, we present comparative analysis of longitudinally sampled blood taken from ferrets and nonhuman primates infected with lethal doses of the Makona variant of Zaire ebolavirus. Strong induction of proinflammatory and prothrombotic signaling programs were present in both ferrets and nonhuman primates, and both transcriptomes were similar to previously published datasets of fatal cases of human Ebola virus infection.
| S-EPMC6249602 | biostudies-literature
Project description:Ebola-infected non-human primates - PBMCs
| PRJNA101297 | ENA
Project description:Infection with Ebola virus (EBOV) causes a fulminant and often fatal hemorrhagic fever. In order to improve our understanding of EBOV pathogenesis and EBOV-host interactions we have examined the molecular features of EBOV infection in vivo. Using self-spotted cDNA microarrays, we analyzed genome-wide host expression patterns in sequential blood samples from nonhuman primates (NHP) infected with EBOV. A reference experiement design type is where all samples are compared to a common reference. Keywords: reference_design
2007-06-28 | GSE8317 | GEO
Project description:Whole blood RNA-Sequencing from 12 Rhesus Macaques following Ebola Makona Infection
| PRJNA476001 | ENA
Project description:Ebola Virus Disease (EVD), caused by the Ebola virus (EBOV), recently made headlines as it cause a large outbreak in West Africa killing more than 11,000 individuals. One aspect of an outbreak of this scale is understanding disease transmission and differences in the host response to infection. In animal models for disease, particularly non-human primate models of disease, a large infectious dose of 1000PFU through intramuscular injection results if a fairly uniformly lethal disease were the animals die after 6-9 days. However, this is not representative of actual transmission routes of infection as humans tend to have variable exposures through cuts and mucosal surfaces and have variable times to death. To determine if a low dose infection through a mucosal surface results in a different host response to infection, we infected 12 cynomologus macaques with 100PFU of EBOV-Makona (EBOV-Mak). To follow the host response to infection, we utilized RNA-Sequencing and a newly developed NanoString codeset to monitor changes in RNA transcripts. We found that despite different onset of disease and some animals presenting with delayed time to death, there was a highly conserved and predictable host response to infection. When animals were aligned based on onset of fever, the first clinical sign of severe disease, the host response to infection was able to be modeled showing a predictable pattern of gene expression with ISG appearing as early as 4 days before fever onset. Together, this shows that lethal EVD has a uniform and predictable response to infection and that expression of a subst of genes is present before the onset of fever.
2018-04-12 | GSE103825 | GEO
Project description:The current outbreak of Ebola virus in West Africa is unprecedented, causing more cases and fatalities than all previous outbreaks combined, and has yet to be controlled. Several post-exposure interventions have been employed under compassionate use to treat patients repatriated to Europe and the United States. However, the in vivo efficacy of these interventions against the new outbreak strain of Ebola virus is unknown. Here we show that lipid-nanoparticle-encapsulated short interfering RNAs (siRNAs) rapidly adapted to target the Makona outbreak strain of Ebola virus are able to protect 100% of rhesus monkeys against lethal challenge when treatment was initiated at 3 days after exposure while animals were viraemic and clinically ill. Although all infected animals showed evidence of advanced disease including abnormal haematology, blood chemistry and coagulopathy, siRNA-treated animals had milder clinical features and fully recovered, while the untreated control animals succumbed to the disease. These results represent the first, to our knowledge, successful demonstration of therapeutic anti-Ebola virus efficacy against the new outbreak strain in nonhuman primates and highlight the rapid development of lipid-nanoparticle-delivered siRNA as a countermeasure against this highly lethal human disease.
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Project description:The family Filoviridae contains three genera, Ebolavirus (EBOV), Marburg virus, and Cuevavirus. Some members of the EBOV genus, including Zaire ebolavirus (ZEBOV), can cause lethal haemorrhagic fever in humans. During 2014 an unprecedented ZEBOV outbreak occurred in West Africa and is still ongoing, resulting in over 10,000 deaths, and causing global concern of uncontrolled disease. To meet this challenge a rapid-acting vaccine is needed. Many vaccine approaches have shown promise in being able to protect nonhuman primates against ZEBOV. In response to the current ZEBOV outbreak several of these vaccines have been fast tracked for human use. However, it is not known whether any of these vaccines can provide protection against the new outbreak Makona strain of ZEBOV. One of these approaches is a first-generation recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing the ZEBOV glycoprotein (GP) (rVSV/ZEBOV). To address safety concerns associated with this vector, we developed two candidate, further-attenuated rVSV/ZEBOV vaccines. Both attenuated vaccines produced an approximately tenfold lower vaccine-associated viraemia compared to the first-generation vaccine and both provided complete, single-dose protection of macaques from lethal challenge with the Makona outbreak strain of ZEBOV.
| S-EPMC4629916 | biostudies-literature
Project description:<p align="left"><b>Title: </b> Ebola-infected non-human primates - PBMCs<br> <p align="left"><b>Summary: </b> Infection with Ebola virus (EBOV) causes a fulminant and often fatal hemorrhagic fever. In order to improve our understanding of EBOV pathogenesis and EBOV-host interactions we have examined the molecular features of EBOV infection in vivo. Using self-spotted cDNA microarrays, we analyzed genome-wide host expression patterns in sequential blood samples from nonhuman primates (NHP) infected with EBOV. <br> <p align="left"><b>Overall Design: </b> Ebola infection of non-human primates (cynomolgus macaques). We took sequential samples of peripheral blood mononuclear cells (PBMC) from 15 cynomolgus macaques infected intramuscularly with 1000 plaque forming units (PFUs) of EBOV, Zaire strain. Peripheral blood samples (2.5mL) were collected on days 1, 4, or 6 prior to infection, in order to define a robust baseline, and then on successive days after infection, until death (immediately prior to euthanasia). Animals were euthanized at days 1, 2, 3, 4, 5, and 6 postinfection. PBMC's were collected at days post-infection as noted, preserved in Trizol, Trizol-extracted total RNA, 1 round amplified (Ambion MessageAmp I), directly labeled by Cy5 incorporation during reverse transcription of amplified RNA. Each blood sample was hybridized versus a common reference. The same reference is used for all samples - Stratagene Universal Human Reference RNA, 1 round of amplification (Ambion MessageAmp I), directly labeled by Cy3 incorporation during reverse transcription of amplified reference RNA. Two to three biological replicates of pre-infection samples were taken for each animal, as well as two to nine biological replicates (from different animals) at each day post-infection. A total of 50 arrays, representing 15 animals is included in this dataset.
2008-03-11 | E-SMDB-4098 | biostudies-arrayexpress