Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Ebola virus glycoprotein variant with increased infectivity for human cells dominated the 2013-2016 outbreak

ABSTRACT: The unprecedented magnitude of the 2013-2016 Makona Ebola virus (M-EBOV) epidemic likely resulted from multiple epidemiologic factors that set it apart from previous outbreaks. Nonetheless, genetic adaptations that distinguish M-EBOV from previous isolates may also have contributed to the scale of the epidemic. Of particular interest is a M-EBOV glycoprotein (GP) variant, GP-A82V, that was first detected at the inflection point of the 2013-2016 outbreak - when the number of cases increased exponentially - and which completely supplanted the earlier M-EBOV sequence. We found that, as compared with the earlier strain, GP-A82V increased the ability of M-EBOV to fuse with and infect cells of primate origin, including human blood dendritic cells, without altering innate immune signaling in target cells. Residue 82 is located at the NPC1-binding site on M-EBOV GP and the increased infectivity of GP-A82V was restricted to cells from species in which the NPC1 orthologue bears primate-defining residues at the critical interface. We utilized HIV-derived lentiviral vectors pseudotyped with founder and A82V containing M-EBOV GPs to explore the potential that this modification alters how human monocyte-derived dendritic cells (MDDCs) respond to EBOV GP stimulation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE84865 | GEO | 2017/08/31

SECONDARY ACCESSION(S): PRJNA335391

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Comparison of Transcriptomic Platform for Analysis of Whole Blood from Ebola-Infected Cynomolgus Macaques

Project description:Ebola virus disease (EVD) is a serious illness associated with 20-90% fatalities. EVD is characterized by robust virus replication and strong host inflammatory immune response. Analyzing the host immune response has increasingly involved multimodal approaches including transcriptomics to profile gene expression. We studied cynomolgus macaques exposed to Ebola virus (EBOV) Makona via different routes with the intent of comparing RNA-Seq to a NanoString nCounter codeset targeting 769 non-human primate (NHP) genes. RNA-Seq analysis of serial blood samples showed different routes led to the same overall transcriptional response seen in previously reported EBOV-exposed NHP studies. Similar profiles were observed using the NanoString codeset. Both platforms displayed a strong correlation in gene expression patterns, thus cross-validating the two methods. This included a strong induction of innate immune response genes at early time points post-infection, and neutrophil-associated genes at later time points. Using data generated from either platform, we could deploy a 41-gene classifier to cluster samples by EBOV infection status. Finally, NanoString and RNA-Seq identified changes in circulating immune cell populations that matched traditional hematology. Together, these results show the complementarity of RNA-Seq and NanoString for gene expression analysis, verifying host biomarkers of infection, and predicting changes in cell types.

2017-11-09 | GSE99463 | GEO

Ebolavirus species associated with differential pathogenicity induce distinct host responses in human macrophages

Project description:Highly pathogenic Zaire ebolavirus (EBOV) infection is associated with a dysregulated immune response and high levels of cytokines and chemokines are observed in fatal human cases. . In stark contrast Reston ebolavirus (RESTV) might be non-pathogenic for humans yet the underlying mechanisms determining pathogenicity for different Ebola viruses are not understood. In this study we investigate antiviral immune responses in EBOV- and RESTV- infected primary human monocyte-derived macrophages (MDM). We provide evidence that increased pathogenicity of the highly pathogenic EBOV is associated with a strong activation of host responses from infected MDM. The observed cytokine response after EBOV infection is strikingly similar to LPS-mediated immune signatures however EBOV caused significant induction of the interferon response in addition. In contrast we show that the low pathogenic RESTV fails to elicit significant immune responses in infected MDM. These results demonstrate a correlation of pathogenicity and excessive MDM activation for different Ebola virus species. Interaction of the viral glycoprotein (GP) with Toll-like receptor 4 (TLR4) leading to activation of NF_B signaling is responsible for this effect rather than differences in replication or blocking of immune signaling. We demonstrate that inhibition of TLR4 is able to abolish EBOV-GP mediated NF_B activation which might offer the possibility to develop targeted treatments for EBOV limiting the extreme immune response that seems to be detrimental to the host.

2016-12-31 | GSE84188 | GEO

Tracking Ebolavirus genomic drift with a resequencing microarray

Project description:This study evaluates a resequencing microarray designed to determine the sequence of the four major genes in the Ebolavirus genome, Nucleoprotein (NP), matrix protein (VP40), glycoprotein (GP) and polymerase (L). The array has the ability to determine the sequence of five species and strains: Zaire Ebolavirus (Mayinga and Makona), Bundibugyo Ebolavirus, Sudan Ebolavirus and Tai Forest Ebolavirus.

2021-01-29 | E-MTAB-10007 | biostudies-arrayexpress

Tracking Ebolavirus genomic drift with a resequencing microarray, verification with NGS

2021-07-02 | E-MTAB-10102 | biostudies-arrayexpress

A systems approach reveals MAVS signaling in myeloid cells as critical in resistance to Ebola virus in murine models of infection

Project description:The unprecedented 2013-16 outbreak of Ebola virus (EBOV) in West Africa resulted in over 11,300 human deaths. Host resistance to EBOV is thought to involve RIG-I-like receptor (RLR) signaling through the adaptor protein, mitochondrial antiviral signaling (MAVS), but role of RLR-MAVS in orchestrating anti-EBOV responses in vivo is not known. Here, we apply a systems approach to MAVS-deficient mice infected with either wild-type or mouse-adapted EBOV. MAVS controlled EBOV replication through expression of IFNα, IFN-stimulated genes, and regulation of inflammatory responses in the spleen, and prevented cell death in the liver, with macrophages implicated as a major cell-type influencing host resistance. A dominant role for RLR signaling in macrophages was confirmed following conditional deletion of MAVS in LysM+ myeloid cells. These findings reveal tissue-specific transcriptional pathways controlled by RLR signaling in resistance to EBOV, and suggest that EBOV adaptation to cause disease in mice is linked in part to increased antagonism of RLR-dependent signaling.

2016-12-31 | GSE83309 | GEO

A conserved transcriptional response to intranasal Ebola virus exposure in nonhuman primates before onset of fever

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

Global gene expression change in the cerebellum of Niemann-Pick disease type C mice with deletion of Ccl3 or Purkinje neuron-specific NPC1 rescue

Project description:Macrophage inflammatory protein 1alpha/CCL3 protein is a known pro-inflammatory cytokine that can mediate chemotaxis of monocytes and promote cell degranulation. Ccl3 gene expression is elevated in the CNS and visceral tissue of many lysosomal storage disorders. The deletion of Ccl3 in a mouse model of Sandhoff disease was reported to result in reduced monocyte-associated pathology in the brain, delayed neurodegeneration, and prolonged health. However, deletion of Ccl3 in a mouse model of Niemann-Pick C disease was dentrimental or neutral instead of beneficial. Prevention of neuronal loss was instead mediated by providing NPC1 to neurons. We used microarrays to detail the global change in gene expression of the cerebellum in Niemann-Pick C disease animals, Niemann-Pick C disease animals with Ccl3 gene deletion, and Niemann-Pick C disease animals with Purkinje neuron-specific NPC1-YFP rescue. To identify the top ~50 genes elevated in NPC disease Npc1-/- (NPC) and Npc1+/- (WT) mice were compared at age P50; To profile changes in gene expression as a result of Ccl3 gene deletion Ccl3-/-;Npc1-/- mice were compared against Npc1-/- mice across various ages; To profile changes in gene expression as a result of Purkinje neuron-sepcific NPC1 rescue P;N;Npc1-/- mice were compared against Npc1-/- mice across various ages.

2012-04-16 | E-GEOD-36119 | biostudies-arrayexpress

Transcription profiling of mouse BALB/c Npc1-/- and Npc1+/+ mutant cerebellum

Project description:Purkinje cells (PC) of the cerebellum degenerate in adult mice with mutations in the Niemann-Pick type C (NPC) disease 1 (Npc1) gene. We subjected BALB/c Npc1+/+ and Npc1-/- mouse cerebella from an early and a later time point of PC degeneration to a genome-wide microarray gene expression analysis. We found general underrepresentation of PC-specific transcripts, consistent with PC loss, and elevated markers of microglia activation at the later time point. Experiment Overall Design: 12 BALB/c Npc1 mice of the two ages P21 and P49 and the two genotypes Npc1+/+ and Npc1-/- were used, 3 replicates for each age and genotype. The animals were of the same breed and lived under identical housing conditions. All except one animal were female. The animals were not further treated, but only sacrificed at P21 or P49.

2008-06-14 | E-GEOD-5944 | biostudies-arrayexpress

Transcript Profiling after a Genetically-induced Elevation of Trehalose 6-Phosphate Reveals a Plethora of Direct and Indirect Responses

Project description:We aim at understanding the Tre6P-specific signalling responses by transiently inducing the expression of the bacterial TPS (otsA) protein at the beginning of the day, leading to an induced rise in Tre6P levels. Treated plants- 2% ethanol spray. non-treated - water spray. empty-vector control - alcR (all previously described in Martins et al. (2013) and in Figueroa et al. (2016).

2023-04-02 | E-MTAB-12783 | biostudies-arrayexpress

Determine whether Streptomyces venezuelae protein SepH (vnz_27360) binds DNA and where

Project description:SepH was identified having a potential role in sporulation following ChIP-seq analysis that showed the sepH gene is under the control of the WhiA and WhiB transcription factors (Bush et al., 2013; Bush et al., 2016). Since SepH has a helix-turn-helix motif, this ChIP-Seq experiment was carried out to determine whether SepH specifically binds DNA and if so, where.

2020-09-30 | E-MTAB-9064 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data