Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Host responses contributing to the attenuation of severe acute respiratory syndrome coronaviruses missing E protein domains

ABSTRACT: Severe acute respiratory syndrome coronavirus (SARS-CoV) causes a respiratory disease leading to death in 10% of the infected people. A mouse adapted SARS-CoV lacking the envelope (E) protein (rSARS-CoV-MA15-ΔE) is attenuated in vivo. To identify E protein domains and host responses that contribute to rSARS-CoV-MA15-ΔE attenuation, several mutants (rSARS-CoV-MA15-E*) containing point mutations or deletions in the amino-terminal or the carboxy-terminal regions of E protein, respectively, were generated. Amino acid substitutions in the amino terminus, or deletion of domains in the internal carboxy terminal region of E protein led to viral attenuation. Attenuated viruses induced minimal lung injury and limited neutrophil influx to the lungs but, interestingly, increased CD4+ and CD8+ T cell counts in BALB/c mice. To analyze the host responses leading to rSARS-CoV-MA15-E* attenuation, the differential gene expression elicited by the native virus and the mutant ones in infected cells was analyzed. The expression levels of a large number of proinflammatory cytokines inducing lung injury was reduced in the lungs of rSARS-CoV-MA15-E* infected mice, whereas the levels of anti-inflammatory cytokines were increased, both at the mRNA and protein levels. These results suggested that the reduction in lung inflammation together with a specific antiviral T cell response, contributed to rSARS-CoV-MA15-E* attenuation. Interestingly, the attenuated viruses completely protected mice against the challenge with the lethal parental virus, being promising vaccine candidates.

ORGANISM(S): Mus musculus

PROVIDER: GSE59185 | GEO | 2015/05/19

SECONDARY ACCESSION(S): PRJNA254698

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Host responses contributing to the attenuation of severe acute respiratory syndrome coronaviruses missing E protein domains

Project description:Severe acute respiratory syndrome coronavirus (SARS-CoV) causes a respiratory disease leading to death in 10% of the infected people. A mouse adapted SARS-CoV lacking the envelope (E) protein (rSARS-CoV-MA15-?E) is attenuated in vivo. To identify E protein domains and host responses that contribute to rSARS-CoV-MA15-?E attenuation, several mutants (rSARS-CoV-MA15-E*) containing point mutations or deletions in the amino-terminal or the carboxy-terminal regions of E protein, respectively, were generated. Amino acid substitutions in the amino terminus, or deletion of domains in the internal carboxy terminal region of E protein led to viral attenuation. Attenuated viruses induced minimal lung injury and limited neutrophil influx to the lungs but, interestingly, increased CD4+ and CD8+ T cell counts in BALB/c mice. To analyze the host responses leading to rSARS-CoV-MA15-E* attenuation, the differential gene expression elicited by the native virus and the mutant ones in infected cells was analyzed. The expression levels of a large number of proinflammatory cytokines inducing lung injury was reduced in the lungs of rSARS-CoV-MA15-E* infected mice, whereas the levels of anti-inflammatory cytokines were increased, both at the mRNA and protein levels. These results suggested that the reduction in lung inflammation together with a specific antiviral T cell response, contributed to rSARS-CoV-MA15-E* attenuation. Interestingly, the attenuated viruses completely protected mice against the challenge with the lethal parental virus, being promising vaccine candidates. Three biological replicates were independently hybridized (one channel per slide) for each sample type (rSARS-CoV-MA15-wt, rSARS-CoV-MA15-?E, rSARS-CoV-MA15-?3, rSARS-CoV-MA15-?5, Mock). Slides were Sure Print G3 Agilent 8x60K Mouse (G4852A-028005)

2015-05-19 | E-GEOD-59185 | biostudies-arrayexpress

SM003 - icSARS CoV, SARS MA15 wild type and SARS BatSRBD mutant virus infections of C57BL6 mice - A time course

Project description:The purpose of this experiment was to investigate the transcriptional differences between mice infected with icSARS CoV, SARS MA15 wild type or SARS BatSRBD viruses. Overview of Experiment: Groups of 20 week old C57BL6 mice were infected with icSARS CoV, Wild Type SARS MA15 or SARS BatSRBD mutant viruses. Infections were done at 10^4 PFU or 10^5 PFU or time-matched mock infected. Time points were 1, 2, 4 and 7 d.p.i. There were 3-5 animals/dose/time point. Lung samples were collected for virus load, transcriptional and proteomics analysis. Weight loss and animal survival were also monitored.

2014-02-15 | E-GEOD-50000 | biostudies-arrayexpress

The PDZ-binding motif of SARS-CoV envelope protein is a determinant of viral pathogenesis

Project description:A recombinant SARS-CoV lacking the envelope (E) protein is attenuated in vivo. Here we report that E protein PDZ-binding motif (PBM), a domain involved in protein-protein interactions, is a major virulence determinant in vivo. Elimination of SARS-CoV E protein PBM by using reverse genetics led to attenuated viruses (SARS-CoV-mutPBM) and to a reduction in the deleterious exacerbate immune response triggered during infection with the parental virus (SARS-CoV-wt). Cellular protein syntenin bound E protein PBM during SARS-CoV infection. Syntenin activates p38 MAPK leading to overexpression of inflammatory cytokines, and we have shown that active p38 MAPK was reduced in lungs of mice infected with SARS-CoVs lacking E protein PBM (SARS-CoV-mutPBM) as compared with the parental virus (SARS-CoV-wt), leading to a decreased expression of inflammatory cytokines and to viral attenuation. Therefore, E protein PBM is a virulence factor that activates pathogenic immune response most likely by using syntenin as a mediator of p38 MAPK induced inflammation. Three biological replicates were independently hybridized (one channel per slide) for each sample type (SARS-CoV-wt, SARS-CoV-mutPBM, Mock). Slides were Sure Print G3 Agilent 8x60K Mouse (G4852A-028005)

2014-10-31 | E-GEOD-52920 | biostudies-arrayexpress

Severe acute respiratory syndrome coronavirus envelope protein regulates cell stress responses and apoptosis

Project description:Severe acute respiratory syndrome virus (SARS-CoV) that lacks the envelope (E) gene (rSARS-CoV-ΔE) is attenuated in vivo [1,2]. To identify factors that contribute to rSARS-CoV-ΔE attenuation, gene expression in cells infected by SARS-CoV with or without E gene was compared. Twenty-five stress response genes were preferentially upregulated during infection in the absence of the E gene. In addition, genes involved in signal transduction, transcription, cell metabolism, immunoregulation, inflammation, apoptosis and cell cycle and differentiation were differentially regulated in cells infected with rSARS-CoV with or without the E gene. Administration of E protein in trans reduced the stress response in cells infected with rSARS-CoV-ΔE, with respiratory syncytial virus, or treated with drugs, such as tunicamycin and thapsigarcin that elicit cell stress by different mechanisms. In addition, SARS-CoV E protein down-regulated the signaling pathway inositol-requiring enzyme 1 (IRE-1) of the unfolded protein response, but not the PKR-like ER kinase (PERK) or activating transcription factor 6 (ATF-6) pathways, and reduced cell apoptosis. Overall, the activation of the IRE-1 pathway was not able to restore cell homeostasis, and apoptosis was induced probably as a meassure to protect the host by limiting virus production and dissemination. The expression of proinflammatory cytokines was reduced in rSARS-CoV-ΔE-infected cells compared to rSARS-CoV-infected cells, suggesting that the increase in stress responses and the reduction of inflammation in the absence of the E gene contributed to the attenuation of rSARS-CoV-ΔE. We used Affymetrix microarrays (Human Genome U133 plus 2.0) to compare global gene expression between SARS-CoV-infected, mock-infected and SARS-CoV-ΔE-infected cells. For ech type of sample three hybridizations were carried-out (independent biological replicates).

2012-06-20 | E-GEOD-30589 | biostudies-arrayexpress

A Single Intranasal Vaccination with a Rationally Attenuated SARS-CoV-2 Elicits Strong Humoral Immune Response and Is Protective in Syrian Hamsters

Project description:Very few live attenuated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are currently in pre-clinical or clinical development. We rationally attenuated SARS-CoV-2 (isolate WA1/2020) by removing the polybasic cleavage site within the spike protein and the open reading frames (ORFs) 6-8, and by introducing a pair of mutations into the non-structural protein 1 (Nsp1). The derived virus (WA1-DPRRA-ORF6-8-Nsp1K164A/H165A) became severely attenuated in both the K18-human ACE2 (hACE2) transgenic mice and in Syrian hamsters. Transcriptomic profiling of nasal turbinates and lung tissues of infected Syrian hamsters confirmed that WA1-DPRRA-ORF6-8-Nsp1K164A/H165A attenuated the upregulation of proinflammatory pathways. A single intranasal immunization of just 100 PFU of the WA1-DPRRA-ORF6-8-Nsp1K164A/H165A elicited binding and neutralizing antibody responses in Syrian hamsters and completely protected against SARS-CoV-2-induced weight loss and pneumonia. These data demonstrate the feasibility of rational attenuation of SARS-CoV-2. WA1-DPRRA-ORF6-8-Nsp1K164A/H165A represents a promising live attenuated vaccine candidate.

2022-04-04 | GSE199922 | GEO

Mouse lung tissue transcriptome response to a mouse-adapted strain of SARS-CoV in wild type C57BL6/NJ mice and TLR3-/- mice

Project description:The purpose is to determine the role of TLR3-/- on the regulation of the host immune response during lethal SARS-CoV infection Groups of 10 week old C57BL6/NJ or TLR3-/- mice were infected with MA15 virus at a dose of 10^5 PFU or time-matched mock infected. Time points were 2, 4 and 7 days post infection. There were 4 or 5 animals/time point. Lung samples were collected for virus load, lung pathology, and transcriptional analysis. Weight loss and animal survival were also monitored.

2015-05-12 | E-GEOD-68820 | biostudies-arrayexpress

SM001: SARS CoV MA15 infection of C57Bl/6 mouse model – Data from 4 viral doses at 1, 2, 4 and 7 days post infection.

Project description:Purpose of experiment was to perform transcriptomic analysis on C57Bl/6 mice infected with different doses of SARS CoV MA15 at 4 different days post infection. Twenty-week-old C57BL/6 mice were infected by intranasal instillation of 10^2, 10^3, 10^4 or 10^5 PFU of SARS CoV MA15 in 50 µl of PBS or mock-infected with PBS alone. At days 1, 2, 4 and 7 days post-infection, lungs were harvested and total RNA was isolated and subjected to microarray analysis. The experimental design was for 4- 5 mice/time point/dose and 3 time-matched mocks. The NIAID Systems Virology Center

2011-11-01 | E-GEOD-33266 | biostudies-arrayexpress

SM003 - icSARS CoV, SARS MA15 wild type and SARS BatSRBD mutant virus infections of C57BL6 mice - A time course

Project description:This purpose of this experiment was to investigate the transcriptional differences between mice infected with icSARS CoV, SARS MA15 wild type or SARS BatSRBD viruses.

2014-02-15 | GSE50000 | GEO

SM001: SARS CoV MA15 infection of C57Bl/6 mouse model – Data from 4 viral doses at 1, 2, 4 and 7 days post infection.

Project description:Purpose of experiment was to perform transcriptomic analysis on C57Bl/6 mice infected with different doses of SARS CoV MA15 at 4 different days post infection.

2011-11-01 | GSE33266 | GEO

The PDZ-binding motif of SARS-CoV envelope protein is a determinant of viral pathogenesis

2014-10-31 | GSE52920 | GEO