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Series GSE59185 Query DataSets for GSE59185
Status Public on May 19, 2015
Title Host responses contributing to the attenuation of severe acute respiratory syndrome coronaviruses missing E protein domains
Organism Mus musculus
Experiment type Expression profiling by array
Summary 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.
 
Overall design 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)
 
Contributor(s) Regla-Nava J, Nieto-Torres JL, Jiménez-Guardeño JM, Fernandez-Delgado R, Fett C, Castaño-Rodríguez C, Perlman S, Enjuanes L, DeDiego ML
Citation(s) 25609816
Submission date Jul 08, 2014
Last update date Jul 19, 2017
Contact name Juan Carlos Oliveros
Organization name CNB, CSIC
Street address Darwin 3
City Cantoblanco
State/province Madrid
ZIP/Postal code 28049
Country Spain
 
Platforms (1)
GPL13912 Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Feature Number version)
Samples (15)
GSM1278210 lung-SARS-CoV-wt-REP1
GSM1278211 lung-SARS-CoV-wt-REP2
GSM1278212 lung-SARS-CoV-wt-REP3
Relations
BioProject PRJNA254698

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE59185_RAW.tar 188.1 Mb (http)(custom) TAR (of TXT)
Raw data provided as supplementary file
Processed data included within Sample table

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